Biomarker |
Gene |
Drug | Tumor Type | Response Description of the effect the treatment has when the tumor is characterized by the specified biomarker | Evidence level Kind of experiment from which the evidence supports the described biomarker | Source Reference supporting the evidenced association | Statement Interpretation or report about the evidenced association |
|---|---|---|---|---|---|---|---|
| biomarker | gene | drug | tumor | response | evidence | source | statement |
| AKT1 E17K |
AKT1 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Both patients with AKT1 E17K alone had primary resistance to cetuximab, whereas 7 of 8 patients with PIK3CA mutation alone experienced tumor shrinkage or stability with anti-EGFR therapy. Thus, AKT1 E17K mutations contribute to primary resistance to cetuximab and serve as an actionable alteration. |
| AKT1 E17K, BRAF WILD TYPE, KRAS WILD TYPE |
AKT1 BRAF KRAS |
Cetuximab, Irinotecan | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, 100% (2/2) colorectal carcinoma patients harboring an AKT1 E17K mutation and wild-type KRAS/BRAF demonstrated resistance to Erbitux (cetuximab) in combination with Camptosar (irinotecan). |
| AKT2 OVEREXPRESSION |
AKT2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Clinical |
Publications Database: CIViC |
In HER2+ metastatic breast cancer treated with trastuzumab (n = 74 patients), the expression of AKT2 and pAkt-Thr308 and/or pAkt-Ser473 localized in nucleus+cytoplasm was associated with an improved time to progression (TTP) and overall survival (OS) compared to AKT2 negative tumors as measured by immunohistochemistry. |
| ANXA1 OVEREXPRESSION |
ANXA1 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis of a Phase III trial, ERBB2 (HER2) positive breast cancer patients with over expression of ANXA1 demonstrated a decreased survival benefit to Herceptin (trastuzumab) compared to treated ERBB2 (HER2) positive breast cancer patients with decreased expression of ANXA1. |
| ANXA1 OVEREXPRESSION, ARID1A AMPLIFICATION |
ANXA1 ARID1A |
Trastuzumab | Breast Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Loss of ARID1A Activates ANXA1, which Serves as a Predictive Biomarker for Trastuzumab Resistance. |
| ANXA1 OVEREXPRESSION, ARID1A ONCOGENIC MUTATION |
ANXA1 ARID1A |
Trastuzumab | Breast Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Loss of ARID1A Activates ANXA1, which Serves as a Predictive Biomarker for Trastuzumab Resistance. |
| ANXA11 R197C |
ANXA11 |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Overall responses for bevacizumab regimens revealed that patients carrying the TT genotype at ANXA11 rs1049550 or at least one G allele at LINS1 rs11247226 seemed greater chemosensitive than those carrying at least one C allele or the AA genotype, respectively (P < 0.05). |
| ANXA11 R197C |
ANXA11 |
Bevacizumab, Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
CONCLUSION: LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed. |
| ARAF S490T |
ARAF |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Phase 1b study of vemurafenib, cetuximab and irinotecan in 19 BRAF V600E mutant colorectal cancer patients. cfDNA panel sequencing was performed in 10 patients after disease progression. One patient had an acquired ARAF S490T mutation that was not identified before treatment initiation. |
| AREG OVEREXPRESSION |
AREG |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
226 cetuximab-treated patients with colorectal cancer (CRC) were analyzed for mRNA expression (by qPCR) of EGFR and its ligands (EGF, TGFA, AREG and EREG). High AREG mRNA expression in KRAS wild type tumours was a favorable predictor in a multivariate analysis (median survival 33 vs. 15 months, p=0.0005). Cetuximab-treated patients with AREG-low KRAS wild type CRC had poor survival, similar to KRAS mutated CRC. |
| AREG OVEREXPRESSION |
AREG |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Prospectively planned retrospective biomarker study in archived tumor tissue from 323 patients from the PICCOLO trial (panitumumab plus irinotecan in CRC patients with KRAS wt). Tumors were classified as high expressor (either EREG or AREG mRNA level) or low expressor (neither EREG nor AREG in top tertile). For RAS wild-type patients with high ligand expression, median PFS was 8.3 [4.0-11.0] months (irinotecan with panitumumab) vs 4.4 [2.8-6.7] months (irinotecan alone); HR, 0.38 [95% CI, 0.24-0.61]; P < .001. In RAS wild-type patients with low ligand expression, median PFS was 3.2 [2.7-8.1] months (irinotecan with panitumumab) vs 4.0 [2.7-7.5] months (irinotecan); HR, 0.93 [95% CI, 0.64-1.37]; P = .73; interaction test results were significant [P = .01]). Results were less clear for response rate (interaction P = .17) and OS (interaction P = .11). |
| AREG OVEREXPRESSION, EREG OVEREXPRESSION |
AREG EREG |
Irinotecan, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis of a Phase I trial, RAS wild-type colorectal cancer patients over expressing AREG and EREG demonstrated a greater PFS (8.3 mo vs 4.4 mo) when treated with a combination of Camptosar (irinotecan) and Vectibix (panitumumab) compared to Camptosar (irinotecan) alone. |
| AREG UNDEREXPRESSION, EREG UNDEREXPRESSION |
AREG EREG |
Irinotecan, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis of a Phase I trial, the combination of Camptosar (irinotecan) and Vectibix (panitumumab) treatment in RAS wild-type colorectal cancer patients with decreased expression of AREG and EREG resulted in a similar PFS (3.2 mo vs 4.0 mo) when compared to Camptosar (irinotecan) alone. |
| ARID1A DELETION |
ARID1A |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, ERBB2 (HER2) positive breast cancer cells with ARID1A loss demonstrated resistance to Herceptin (trastuzumab) in culture. |
| ARID1A DELETION, ERBB2 AMPLIFICATION |
ARID1A ERBB2 |
MK2206, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a breast cancer cell line with ARID1A loss and harboring ERBB2 (HER2) amplification demonstrated restored sensitivity to Herceptin (trastuzumab) when additionally treated with MK2206 in culture. |
| ATN1 UNDEREXPRESSION, BRAF WILD TYPE, KRAS WILD TYPE |
ATN1 BRAF KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, ATN1 mRNA level was decreased in the progressive disease group compared to the disease control group in KRAS and BRAF wild-type colorectal cancer patients treated with Erbitux (cetuximab) or Vectibix (panitumumab), which supported its potential role as a predictive marker for treatment response. |
| ATN1 UNDEREXPRESSION, BRAF WILD TYPE, KRAS WILD TYPE |
ATN1 BRAF KRAS |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, ATN1 mRNA level was decreased in the progressive disease group compared to the disease control group in KRAS and BRAF wild-type colorectal cancer patients treated with Erbitux (cetuximab) or Vectibix (panitumumab), which supported its potential role as a predictive marker for treatment response. |
| BIRC5 OVEREXPRESSION |
BIRC5 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
13 HER2 breast cancer patients were treated with trastuzumab and then trastuzumab + docetaxel prior to surgery. Pretreatment biopsies and post-treatment surgical samples were obtained, and microarray performed. 5 of 13 patients responded to treatment, and pretreatment biopsies from non-responders showed significantly higher survivin (BIRC5) mRNA (p=0.026) levels than responders. In HER2 positive, trastuzumab-sensitive BT474 cells, overexpression of survivin blunted sensitivity to trastuzumab. In HER2 positive trastuzumab-resistant breast cancer cell lines, knockdown of survivin with RNAi or with YM155 induced growth inhibition and apoptosis. |
| BRAF AMPLIFICATION |
BRAF |
Dabrafenib, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Paired pre-treatment and post-progression tumor biopsies from BRAF-mutant CRC patients treated with RAF inhibitor combinations were analyzed. Alterations in MAPK pathway genes were found in resistant tumors not present in matched pre-treatment tumors, including KRAS amplification, BRAF amplification, and a MEK1 mutation. |
| BRAF AMPLIFICATION, BRAF V600E |
BRAF |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired BRAF V600E amplification. |
| BRAF AMPLIFICATION, BRAF V600E |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF D594G |
BRAF |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 53, KRAS exon 2 wild-type, metastatic colorectal cancer patients, patients harboring BRAF G466A (n=1), G469A (n=2), D594G (n=1), or V600E (n=2) mutations were reported to be non-responders to cetuximab in combination with irinotecan, (BRAF mutation positive: responders vs. non-responders = 0 vs. 6; BRAF wild-type: responders vs. non-responders 30 vs. 17; P=0.004), as compared to patients with wild-type BRAF. |
| BRAF D594G |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Two patients with stage IV BRAF (D594G) mutations received anti-EGFR antibody therapy (cetuximab and panitumumab). The first patient was on FOLFOX plus bevacizumab and showed no signs of progression for 10 months. No response was observed after cetuximab was given as a third line therapy. The second patient received panitumumab with FOLFOX and showed no signs of progression for 8 months with reduction of the size of metastases. |
| BRAF G466V |
BRAF |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, treatment with Erbitux (cetuximab) reduced ERK signaling and resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1. |
| BRAF G466V |
BRAF |
Irinotecan, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, a patient with metastatic colorectal cancer harboring BRAF G466V, and with wild-type RAS and NF1, demonstrated tumor regression following treatment with Vectibix (panitumumab) plus Camptosar (irinotecan). |
| BRAF G596V, NRAS G13R |
BRAF NRAS |
Cetuximab, LSN3074753 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in a patient-derived xenograft model of colorectal cancer harboring BRAF G596V and NRAS G13R. |
| BRAF MUTATION |
BRAF |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks. |
| BRAF MUTATION |
BRAF |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed a response to cetuximab whereas 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. |
| BRAF MUTATION |
BRAF |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks. |
| BRAF MUTATION |
BRAF |
Cetuximab, LSN3074753 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12). |
| BRAF MUTATION |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
A quantitative synthesis was performed on nine studies comparing treatment of metastatic colorectal cancer with cetuximab or panitumumab and chemotherapy, versus chemotherapy alone, or with other targeted inhibitors. It was found that in the patient subgroup with BRAF mutation (V600E in the majority of cases), there were no benefits to overall survival, progression free survival, or overall response rate with addition of cetuximab or panitumumab to treatment. This conclusion held in the first line treatment as well as general treatment setting. |
| BRAF MUTATION |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer. |
| BRAF NON-V600E MUTATION |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort. The median PFS in BRAF(non-V600E) mutations was 2.4 months, similar to that in RAS or BRAF(V600E) mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months). Although BRAF(non-V600E) mutations identified were a rare and unestablished molecular subtype, certain BRAF(non-V600E) mutations might contribute to a lesser benefit of anti-EGFR monoclonal antibody treatment. |
| BRAF V600 |
BRAF |
Alpelisib (BYL719), Dabrafenib, Panitumumab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
These results indicate that combination treatment of encorafenib and cetuximab ± BYL719 is well tolerated with promising antitumor activity in pts with advanced BRAFm CRC who failed standard treatment. |
| BRAF V600 |
BRAF |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation. |
| BRAF V600 |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Patients with BRAF-V600 mutated cancers were identified (n=122) and subsequently underwent targeted therapy. 27 patients with colorectal cancer were treated with vemurafenib and cetuximab (N=24 with BRAF V600E mutation, N=3 with V600 unknown status). One response was observed; however, approximately half the patients had tumor regression that did not meet the standard criteria for a partial response. Median progression-free survival and overall survival for patients receiving combination therapy were 3.7 months (95% CI, 1.8 to 5.1) and 7.1 months (95% CI, 4.4 to not reached), respectively. Patients were heavily pretreated, with a median of two lines of previous therapy (range, one to six). |
| BRAF V600 |
BRAF |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In metastatic colorectal cancer patients with wildtype KRAS, BRAF mutations were associated with poor progression free survival regardless of treatment (panitumumab with best supportive care or best supportive care alone). |
| BRAF V600E |
BRAF |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
BGB-283, Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, BGB-283 in combination with Erbitux (cetuximab) demonstrated enhanced tumor suppression in colorectal cancer cell line xenograft models harboring BRAF V600E. |
| BRAF V600E |
BRAF |
BI 882370, Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Erbitux (cetuximab) in xenograft models, resulting in tumor growth inhibition and partial tumor regression. |
| BRAF V600E |
BRAF |
Bevacizumab, Capecitabine, Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Mouse xenografts using HT29 cells harboring the BRAF V600E mutation treated with combination therapy (capecitabine, vemurafenib, bevacizumab) showed increased survival and reduced tumor burden compared to single and double agent therapies. |
| BRAF V600E |
BRAF |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| BRAF V600E |
BRAF |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 148 treatment naive metastatic colorectal cancer patients, patients with BRAF V600E (n=14) mutation treated with FOLFOX4 plus cetuximab were associated with a decreased progression free survival (7.2mo vs. 9.7mo, HR:0.39, 95% CI:0.21-0.72, P=0.0017), and decreased overall survival (11.7mo vs. 28.5mo, HR:0.23, 95% CI:0.12-0.41, P<0.0001), as compared to patients with wildtype BRAF. |
| BRAF V600E |
BRAF |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Chemotherapy-refractory patients with colorectal cancer harboring BRAF mutations had lower response and disease control rates as well as shorter progression free and overall survival following cetuximab plus chemotherapy than those with wildtype BRAF. |
| BRAF V600E |
BRAF |
Cetuximab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Erbitux (cetuximab) is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). |
| BRAF V600E |
BRAF |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Dabrafenib, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Erlotinib, Gefitinib, Vemurafenib | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Inhibition of the BRAF(V600E) oncoprotein by the small-molecule drug PLX4032 (vemurafenib) is highly effective in the treatment of melanoma. Our data suggest that BRAF(V600E) mutant colon cancers (approximately 8-10% of all colon cancers), for which there are currently no targeted treatment options available, might benefit from combination therapy consisting of BRAF and EGFR inhibitors. |
| BRAF V600E |
BRAF |
Cetuximab, Gefitinib, Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
5 of 7 colorectal cancer (CRC) cell lines with BRAF V600E mutation were resistant to treatment with the BRAF inhibitor vemurafenib. An RNAi screen in the WiDr cell line (a V600E CRC line) identified EGFR as an enhancer for survival when exposed to vemurafenib. Treatment with vemurafenib and EGFR inhibitor (cetuximab or gefitinib) in V600E CRC cells (WiDr, VACO432 and KM20) showed inhibited growth as well as induction of the cleaved PARP apoptotic marker. WiDr and VACO432 cells were injected into immunodeficient mice. Modest response was seen with vemurafenib treatment, while combination treatment showed considerable tumor growth inhibition as compared to control. |
| BRAF V600E |
BRAF |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Phase 1b study of vemurafenib, cetuximab and irinotecan in 19 patients with colorectal cancer (1 with appendiceal cancer). Six of 17 evaluable patients achieved an objective response, 15 patients total had either stable disease or radiographic response (the patient with appendiceal cancer had disease progression). Estimated median PFS was 7.7 months. Effect of the combined treatment was also observed in xenograft and cell line studies. |
| BRAF V600E |
BRAF |
Cetuximab, Irinotecan, Vemurafenib | Malignant Colon Neoplasm | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Zelboraf (vemurafenib), Erbitux (cetuximab), and Camptosar (irinotecan) combination therapy is included in guidelines for advanced or metastatic colon cancer patients harboring BRAF V600E (NCCN.org). |
| BRAF V600E |
BRAF |
Cetuximab, PLX4720 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of PLX4720 and Erbitux (cetuximab) inhibited tumor growth in colorectal cancer cell line xenograft models harboring BRAF V600E. |
| BRAF V600E |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
This meta-analysis of 7 randomized control trials evaluating overall survival (OS) (8 for progression free survival) could not definitely state that survival benefit of anti-EGFR monoclonal antibodies is limited to patients with wild type BRAF. In other words, the authors believe that there is insufficient data to justify the exclusion of anti-EGFR monoclonal antibody therapy for patients with mutant BRAF. In these studies, mutant BRAF specifically meant the V600E mutation. |
| BRAF V600E |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort. The median PFS in BRAF(non-V600E) mutations was 2.4 months, similar to that in RAS or BRAF(V600E) mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months). |
| BRAF V600E |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In metastatic colorectal cancer patients with wildtype KRAS status, those with a BRAF V600E mutation were less likely to respond to treatment with cetuximab or panitumumab than those with wildtype BRAF (0% vs. 32% , P=0.029). Regardless of KRAS status, patients with BRAF mutations had reduced progression-free and overall survival (P=0.0107 and P <0.0001, respectively). Transfection of the colorectal cancer cell line DiFi with a BRAF V600E expression vector conferred decreased sensitivity to cetuximab and panitumumab in comparison to cells transfected with empty vector. |
| BRAF V600E |
BRAF |
Cetuximab, Panitumumab, Sorafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
The effect of the BRAF V600E mutation on cetuximab or panitumumab response was also assessed using cellular models of CRC. Treatment with the BRAF inhibitor sorafenib restored sensitivity to panitumumab or cetuximab of CRC cells carrying the V600E allele. |
| BRAF V600E |
BRAF |
Cetuximab, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Sorafenib | Colon Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Sorafenib and cetuximab therapy led to a mixed radiographic response with some areas showing dramatic improvement and other areas showing stable disease over a 7-month period which is a notably long period of progression-free survival for V600E BRAF mutated colon cancer. |
| BRAF V600E |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Zelboraf (vemurafenib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) was tolerated and showed clinical benefit in a patient with BRAF V600E mutant colorectal cancer. |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, treatment with the combination of Vectibix (panitumumab) and Tafinlar (dabrafenib) resulted in stable disease in 7/8 colorectal cancer patients harboring a BRAF V600E mutation (J Clin Oncol 32:5s, 2014 (suppl; abstr 3515)). |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib) and Vectibix (panitumumab) resulted in an overall response rate of 10% (2/20, 1 complete response, 1 partial response), stable disease in 80% (16/20), and a median progression-free survival of 3.5 months in patients with BRAF V600E colorectal cancer. |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Efficacy and tolerability in an open-label phase I/II study of MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in combination in patients (pts) with BRAF V600E mutated colorectal cancer (CRC). P can be safely combined with D or D/T. Encouraging evidence of clinical activity has been seen.// Updated efficacy of the MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in patients (pts) with BRAF V600E mutated (BRAFm) metastatic colorectal cancer (mCRC).Encouraging clinical activity with acceptable tolerability is seen with the triplet D+T+P in BRAFm mCRC. |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this trial, 142 patients with metastatic, BRAF V600E mutant colorectal cancer were randomized to receive either BRAF inhibitor dabrafenib (D) + EGFR inhibitor panitumumab (P); or a triple therapy of D + P and MEK inhibition with trametinib (T) or T + P. Confirmed response rates for D+P (n=20), D+T+P (n=91), and T+P (n=31) were 10%, 21%, and 0%, respectively. |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in an overall response rate of 21% (19/91, 1 complete response, 18 partial response), stable disease in 65% (59/91), and a median progression-free survival of 4.2 months in patients with BRAF V600E colorectal cancer. |
| BRAF V600E |
BRAF |
Irinotecan, Panitumumab, Vemurafenib | Malignant Colon Neoplasm | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Zelboraf (vemurafenib), Vectibix (panitumumab), and Irinotecan combination therapy is included in guidelines for advanced or metastatic colon cancer patients harboring BRAF V600E (NCCN.org). |
| BRAF V600E |
BRAF |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| BRAF V600E |
BRAF |
Panitumumab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Vectibix (panitumumab) is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). |
| BRAF V600E |
BRAF |
Panitumumab, Sorafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Cetuximab or panitumumab may be ineffective in patients with BRAF mutation unless BRAF inhibitor such as Sorafenib is introduced. |
| BRAF V600E |
BRAF |
Panitumumab, Trametinib | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this trial, 142 patients with metastatic, BRAF V600E mutant colorectal cancer were randomized to receive either BRAF inhibitor dabrafenib (D) + EGFR inhibitor panitumumab (P); or a triple therapy of D + P and MEK inhibition with trametinib (T) or T + P. Confirmed response rates for D+P (n=20), D+T+P (n=91), and T+P (n=31) were 10%, 21%, and 0%, respectively. |
| BRAF V600E |
BRAF |
Panitumumab, Trametinib | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination therapy consisting of Vectibix (panitumumab) and Mekinist (trametinib) resulted in an overall response rate of 0% (0/31), stable disease in 55% (17/31), and a median progression-free survival of 2.6 months in patients with BRAF V600E colorectal cancer. |
| BRAF V600E |
BRAF |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, 83% (10/12) of patients with colorectal cancer carrying a BRAF V600E mutation demonstrated tumor regression when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab). |
| BRAF V600E |
BRAF |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Case report of a patient with BRAF V600E mutant metastatic colorectal cancer. Combined EGFR and BRAF inhibition (panitumumab and vemurafenib) showed an initial partial response for 4 months with subsequent disease progression. |
| BRAF V600E |
BRAF |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Treatment response to mutant BRAF inhibitor vemurafenib and EGFR inhibitor panitumumab was assayed in 12 patients with metastatic colorectal cancer (CRC) who had progressed on chemotherapy. Two patients had confirmed partial responses, and 2 showed stable disease over 6 months. The authors conclude that although some efficacy is seen, only a small subset of patients respond to this treatment and the responses are not durable. |
| BRAF V600E MSI HIGH |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in improved response rate (46%, 5/11 vs 27%, 18/67) and progression-free survival (HR=2.64, p=0.0449) in BRAF V600E mutant colorectal cancer patients with MSI-high/MMR-deficient tumors, compared to patients with MSS/MMR-proficient tumors. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Dabrafenib, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Selumetinib (AZD6244), Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Selumetinib (AZD6244), and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture. |
| BRAF V600E, EGFR AMPLIFICATION, EGFR S492R |
BRAF EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colorectal cancer patient harboring EGFR amplification, BRAF V600E, and EGFR S492R demonstrated resistance to Erbitux (cetuximab). |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Erbitux (cetuximab) in culture. |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Cetuximab, Dabrafenib, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquired secondary resistance mutation of EGFR G465R. |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Vectibix (panitumumab) in culture. |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment in culture. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to combination treatment consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture, likely due to the acquisition of KRAS A146V and A146T secondary resistance mutations. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) in culture. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) in culture. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS AMPLIFICATION |
BRAF KRAS |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired KRAS amplification. |
| BRAF V600E, KRAS AMPLIFICATION |
BRAF KRAS |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture. |
| BRAF V600E, KRAS AMPLIFICATION |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS G12D |
BRAF KRAS |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture. |
| BRAF V600E, KRAS G12D |
BRAF KRAS |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS G12D |
BRAF KRAS |
Cetuximab, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS G12D |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquisition of KRAS G12D. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquisition of KRAS G13D. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, SCH772984 | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and SCH772984 in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS WILD TYPE |
BRAF KRAS |
Cetuximab, Irinotecan | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Also, BRAF V600E mutation has been associated with resistance. METHODS: We investigated the role of KRAS codons 61 and 146 and BRAF V600E mutations in predicting resistance to cetuximab plus irinotecan in a cohort of KRAS codons 12 and 13 wild-type patients. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Dabrafenib, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 V211D |
BRAF MAP2K1 |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture. |
| BRAF V600E, MAP2K1 V211D |
BRAF MAP2K1 |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture. |
| BRAF V600E, MAP2K1 V211D |
BRAF MAP2K1 |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired secondary resistant mutation of MAP2K1 V211D. |
| BRAF V600E, MDM2 AMPLIFICATION, MET AMPLIFICATION |
BRAF MDM2 MET |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, a colorectal cancer patient harboring BRAF V600E, eventually developed resistance to Vectibix (panitumumab) and Zelboraf (vemurafenib) due to acquiring amplification of MET and MDM2. |
| BRAF V600E, MET AMPLIFICATION |
BRAF MET |
Panitumumab, Vemurafenib | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
MET-Driven Resistance to Dual EGFR and BRAF Blockade May Be Overcome by Switching from EGFR to MET Inhibition in BRAF-Mutated Colorectal Cancer. |
| BRAF V600E, PIK3CA P449T |
BRAF PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Erbitux (cetuximab) in culture. |
| BRAF V600E, PIK3CA P449T |
BRAF PIK3CA |
Cetuximab, Regorafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring BRAF V600E and PIK3CA P449T in culture. |
| BRAF V600E, TP53 Q192K |
BRAF TP53 |
Panitumumab, Vemurafenib | Malignant Colon Neoplasm | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colon cancer patient harboring BRAF V600E and TP53 Q192K demonstrated a partial response when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab). |
| BRAF V600X |
BRAF |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib trial, the addition of Zelboraf (vemurafenib) to Camptosar (irinotecan) plus Erbitux (cetuximab) improved progression-free survival (4.4 mo vs. 2.0 mo), and disease control rate (67% vs. 22%), compared to Camptosar (irinotecan) plus Erbitux (cetuximab) without Zelboraf (vemurafenib), in patients with BRAF V600-mutant colorectal cancer (J Clin Oncol 35, 2017 (suppl 4S; abstract 520)). |
| BRAF V600X |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II clinical trial, treatment with the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) resulted in an overall response rate of 4% (1/26), stable disease in 69% (18/26), and a median progression-free survival of 3.7 months in patients with BRAF V600-mutant colorectal cancer. |
| BRAF WILD TYPE, KRAS WILD TYPE, NRAS WILD TYPE |
BRAF KRAS NRAS |
Bevacizumab, Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial (MACBETH), first-line treatment with the combination of Erbitux (cetuximab) and FOLFIRI, followed by Avastin (bevacizumab) maintenance, demonstrated activity in BRAF/KRAS/NRAS wild-type metastatic colorectal cancer patients, resulting in a median overall survival in the intent-to-treat population of 32.2 mo and response rate of 75% (43/57), however, resulted in a 10-mo PFS rate of 40.4% (23/57), which did not meet the primary endpoint of 70%. |
| BRAF WILD TYPE, KRAS WILD TYPE, NRAS WILD TYPE |
BRAF KRAS NRAS |
Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial (MACBETH), first-line treatment with the combination of Erbitux (cetuximab) and FOLFIRI, followed by Erbitux (cetuximab) maintenance, demonstrated activity in BRAF/KRAS/NRAS wild-type metastatic colorectal cancer patients, resulting in a median overall survival in the intent-to-treat population of 33.2 mo and response rate of 68% (40/59), however, resulted in a 10-mo PFS rate of 50.8% (30/59), which did not meet the primary endpoint of 70%. |
| BRAF WILD TYPE, KRAS WILD TYPE, NRAS WILD TYPE, PIK3CA WILD TYPE |
BRAF KRAS NRAS PIK3CA |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) inhibited growth of human colorectal cancer cells wild-type for BRAF, KRAS, NRAS and PIK3CA in culture. |
| BRAF WILD TYPE, KRAS WILD TYPE, NRAS WILD TYPE, PIK3CA WILD TYPE |
BRAF KRAS NRAS PIK3CA |
Cetuximab, FOLFOX | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial, Erbitux (cetuximab) in combination with FOLFOX resulted in improved median progression-free survival (6.9 months) comparing to FOLFOX alone (5.3 months) in BRAF, KRAS, NRAS, and PIK3CA wild-type colorectal cancer patients (hazard ratio =0.56). |
| BRAF WILD TYPE, KRAS WILD TYPE, PIK3CA MUTATION |
BRAF KRAS PIK3CA |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, Erbitux (cetuximab) treatment, alone or in combination, resulted in disease regression or stable disease in 88% (7/8) KRAS/BRAF-wild type colorectal carcinoma patients harboring a PIK3CA mutation. |
| CCND1 OVEREXPRESSION |
CCND1 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, treatment with Herceptin (trastuzumab) resulted in a decreased response in ERBB2 (HER2) receptor positive breast cancer cells with induced overexpression of CCND1 in culture. |
| EGFR AMPLIFICATION |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
87 patients with metastatic colorectal cancer treated with cetuximab were retrospectively analyzed for EGFR amplifications by FISH. In multivariate analysis, EGFR amplification predicted response and overall survival independent of KRAS status. |
| EGFR AMPLIFICATION |
EGFR |
Cetuximab, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this meta-analysis (14 studies, 1021 patients), EGFR gene copy number (GCN) was predictive of improved progression free survival (PFS) and overall survival (OS) with cetuximab or panitumumab regardless of KRAS status. For the pooled analysis, the objective response rate (ORR) was 65.2% (167/256) in patients with high EFGR GCN, while in patients with low EFGR GCN, the pooled ORR was 12.2% (44/361). The odds ratio (OR) was 6.905 (95% CI: 4.489-10.620; Z=8.79, P=0.000). In wild type KRAS patients, the pooled OR was 8.133 (95% CI: 4.316-15.326; Z=6.48, P=0.000). |
| EGFR AMPLIFICATION |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III study, response to Vectibix (pantitumumab) was associated with EGFR amplification in colorectal cancer patients. |
| EGFR AMPLIFICATION, EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colorectal cancer patient harboring EGFR amplification and EGFR S492R demonstrated resistance to Erbitux (cetuximab). |
| EGFR AMPLIFICATION, EGFR S492R |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colorectal cancer patient harboring both EGFR amplification and EGFR S492R demonstrated a 50% tumor reduction when treated with Vectibix (panitumumab). |
| EGFR EXPRESSION |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Patients with refractory colorectal cancer expressing immunohistochemically detectable EGFR were randomly assigned to receive treatment with cetuximab (n=287) or receive supportive care alone (n=285). Patients receiving cetuximab had increased overall survival (HR=0.77, 95%CI 0.64-0.92; p=0.005), increased progression-free survival (HR=0.68, 95%CI 0.57-0.80; p<0.001), and improved quality of life at 4 months measured by survey on physical deterioration (-5.9 vs -12.5; p=0.03) and global health status (-3.6 vs. -15.2; p<0.001). |
| EGFR EXPRESSION |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
57 patients with chemorefractory colorectal cancer expressing EGFR (IHC staining) were treated with single-agent cetuximab in this phase 2 study. Five patients (9%; 95% CI, 3% to 19%) achieved a partial response. Twenty-one additional patients had stable disease or minor responses. The median survival in these previously treated patients with chemotherapy-refractory colorectal cancer was 6.4 months. |
| EGFR EXPRESSION |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
463 patients with 1% or more EGFR tumor cell membrane staining, with metastatic CRC progressive after standard chemotherapy were randomized to panitumumab plus best supportive care (BSC, n = 231) or BSC alone (n = 232). Panitumumab significantly prolonged PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66, [P < .0001]). Objective response rates favored panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10% for panitumumab and 0% for BSC (P < .0001). No difference was observed in OS (HR, 1.00; 95% CI, 0.82 to 1.22), but 76% of BSC patients entered the cross-over study. |
| EGFR EXPRESSION, KRAS WILD TYPE |
EGFR KRAS |
Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial that supported FDA approval, the combination of Erbitux (cetuximab) and FOLFIRI resulted in a greater tumor response rate in EGFR positive, KRAS wild-type colorectal cancer patients (59% (102/172)) compared to EGFR positive, KRAS mutant colorectal cancer patients (36.2% (38/105)). |
| EGFR G465E |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR G465E were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR G465E |
EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR G465E were resistant to Vectibix (panitumumab)-induced growth inhibition in culture. |
| EGFR G465R |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Preclinical |
Publications Database: CGI |
Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. |
| EGFR G465R |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Epidermal growth factor receptor mutation mediates cross-resistance to panitumumab and cetuximab in gastrointestinal cancer.// Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.// Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR. |
| EGFR G465R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR G465R were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR G465R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Mutational profiling of cetuximab-resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR alleles: S464L, G465R, and I491M. |
| EGFR G465R |
EGFR |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
An EGFR G465R mutation (22% of mutant alleles) was detected in a biopsy from one patient which had been previously treated with cetuximab in the analysis of 15 patients with refractory, metastatic CRC after cetuximab/panitumumab, prior to Sym004 treatment. Treatment of this patient with Sym004 yielded disease stabilization lasting 15 weeks. Sym004 is a 1:1 mixture of two non-overlapping anti-EGFR monoclonal antibodies. In vitro analysis in the murine fibroblast cell line NIH3T3 with ectopic expression of EGFR mutations S492R, R451C, K467T, and G465R showed that Sym004 effectively bound to all mutants, whereas cetuximab and panitumumab did not effectively bind to all mutants. In-vitro, Sym004 inhibited growth of S492R and G465R EGFR mutant cell lines. In-vivo analysis of S492R and G465R mutant cell lines showed regression of S492R and tumor growth delay of G465R mutant cell lines. G465R mutant cell lines were resistant to treatment with panitumumab or cetuximab in-vitro. |
| EGFR G465R |
EGFR |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Epidermal growth factor receptor mutation mediates cross-resistance to panitumumab and cetuximab in gastrointestinal cancer. |
| EGFR G465R |
EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR G465R were resistant to Vectibix (panitumumab)-induced growth inhibition in culture. |
| EGFR G719S |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: ResCur |
CONCLUSION: The colon-cancer derived G719S and G724S mutants are oncogenic and sensitive in vitro to cetuximab. |
| EGFR G719S |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Whole genome sequencing of a case of colon carcinoma revealed a G724S mutation in the EGFR gene. In-vitro, this mutation was shown to be oncogenic and sensitive to Cetuximab, yet relatively insensitive towards small molecules. The same in-vitro results could be reproduced for the G719S mutation. |
| EGFR G724S |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab. We show that G724S mutant EGFR is oncogenic and that it differs from classic lung cancer derived EGFR mutants in that it is cetuximab responsive in vitro, yet relatively insensitive to small molecule kinase inhibitors. CONCLUSION: The colon-cancer derived G719S and G724S mutants are oncogenic and sensitive in vitro to cetuximab. |
| EGFR G724S |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Whole genome sequencing of a case of colon carcinoma revealed a G724S mutation in the EGFR gene. In-vitro, this mutation was shown to be oncogenic and sensitive to Cetuximab, yet relatively insensitive towards small molecules. |
| EGFR I491M |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Preclinical |
Publications Database: CGI |
Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. |
| EGFR I491M |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR I491M were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR I491M |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Mutational profiling of cetuximab-resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR alleles: S464L, G465R, and I491M. |
| EGFR I491M |
EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR I491M were resistant to Vectibix (panitumumab)-induced growth inhibition in culture. |
| EGFR K467T |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.// Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR. |
| EGFR K467T |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR K467T were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR K467T |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
In this preclinical study on the effects of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. In NIH3T3 cells expressing EGFR with a K467T mutation, Sym004 and panitumumab bound the mutated receptor and inhibited EGFR phosphorylation in the presence of ligand while cetuximab neither bound to nor inhibited EGFR phosphorylation of the mutated receptor. |
| EGFR K467T |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Vectibix (panitumumab) inhibited survival of colorectal cancer cell lines over expressing EGFR K467T in culture. |
| EGFR K467T |
EGFR |
Panitumumab, Sym004 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In this preclinical study on the effects of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. In NIH3T3 cells expressing EGFR with a K467T mutation, Sym004 and panitumumab bound the mutated receptor and inhibited EGFR phosphorylation in the presence of ligand while cetuximab neither bound to nor inhibited EGFR phosphorylation of the mutated receptor. |
| EGFR OVEREXPRESSION |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| EGFR OVEREXPRESSION |
EGFR |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| EGFR R451C |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.// Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR. |
| EGFR R451C |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) inhibited survival of colorectal cancer cell lines over expressing EGFR R451C in culture. |
| EGFR R451C |
EGFR |
Cetuximab, Panitumumab, Sym004 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In this preclinical study on the effects of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. The R451C mutation showed moderate drug-receptor binding with sym004, cetuximab and panitumumab treatment and inhibition of EGFR phosphorylation. |
| EGFR R451C |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Vectibix (panitumumab) inhibited survival of colorectal cancer cell lines over expressing EGFR R451C in culture. |
| EGFR R521K |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Allele Frequencies of the Epidermal Growth Factor Receptors Polymorphism R521K in Colorectal Cancer Patients and Healthy Subjects Indicate a Risk-Reducing Effect of K521 in Syrian Population. Studies showed the polymorphism [R521K] G A in the EGFR gene to be involved in both colorectal cancer susceptibility and clinical response to therapeutics (e.g., Cetuximab). |
| EGFR S464L |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Preclinical |
Publications Database: CGI |
Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. |
| EGFR S464L |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Mutational profiling of cetuximab-resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR alleles: S464L, G465R, and I491M. |
| EGFR S464L |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR S464L were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR S464L |
EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR S464L were resistant to Vectibix (panitumumab)-induced growth inhibition in culture. |
| EGFR S468R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Extracellular S468R mutation of the epidermal growth factor receptor (EGFR) was recently identified as the cause of resistance to cetuximab, a widely used drug in colorectal cancer treatment. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer.// Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.// Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In-vitro studies found this mutation to confer resistance to cetuximab. 2 of 10 patients studied also harbored EGFR S492R and were resistant to cetuximab therapy. Panitumumab was still active in-vitro and in one patient. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
In this preclinical study of the effects of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. The S492R mutation was sensitive to Sym004 and panitumumab treatment but resistant to cetuximab. Experiments include flow cytometry binding assay, kinase phosphorylation, cell viability, downstream signalling. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
MET gene amplification emerged in 1 patient during Sym004 treatment, and a partial response was seen in a patient with EGFR(S492R) mutation that is predictive of cetuximab resistance. MET gene amplification emerged in 1 patient during Sym004 treatment, and a partial response was seen in a patient with EGFR(S492R) mutation that is predictive of cetuximab resistance. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR S492R were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
We describe an acquired EGFR ectodomain mutation (S492R) that prevents cetuximab binding and confers resistance to cetuximab. A subject with cetuximab resistance harboring the S492R mutation responded to treatment with panitumumab. |
| EGFR S492R |
EGFR |
Panitumumab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer. |
| EGFR S492R |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Vectibix (panitumumab) inhibited survival of colorectal cancer cell lines over expressing EGFR S492R in culture. |
| EGFR S492R |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
We describe an acquired EGFR ectodomain mutation (S492R) that prevents cetuximab binding and confers resistance to cetuximab. A subject with cetuximab resistance harboring the S492R mutation responded to treatment with panitumumab. |
| EGFR S492R |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Tumor sequencing in pre- and post-therapy specimens from ten individuals with mCRC who experienced disease progression after a prior response to cetuximab with chemotherapy was performed. The S492R mutation was identified in two persons. One of them had already died, the other received treatment with panitumumab and had a partial response (50% tumor reduction in all liver lesions) for 5 months. |
| EGFR S492R |
EGFR |
Panitumumab, Sym004 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In this preclinical study of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. The S492R mutation was sensitive to Sym004 and panitumumab treatment but resistant to cetuximab. Experiments include flow cytometry binding assay, kinase phosphorylation, cell viability, downstream signalling. |
| EPHB4 OVEREXPRESSION |
EPHB4 |
Bevacizumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
EPHB4 expression, as assessed by quantitative RT-PCR in 13 colorectal cancer patients treated with bevacizumab, was higher in non-responders (p = 0.048). No difference was observed in a control group without bevacizumab treatment. qRT-PCR results were also shown to correlate with protein expression measured by IHC. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Afatinib, Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this phase 2 trial, treatment-naive, ERBB2-positive (by IHC) breast cancer patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to afatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). The primary end point was objective response rate. Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatment of HER2-positive breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Afatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Trastuzumab resistance is thought to consist of multiple compensatory mechanisms involving ErbB family members such as increased signaling through ErbB family heterodimers. The irreversible TKI afatinib blocks EGFR, HER2, ErbB3 and ErbB4. Thus afatinib was studied in this Phase I trial of trastuzumab-progressed HER2 positive metastatic BC (MBC) in combination with continued trastuzumab treatment, where trastuzumab is still the perferred treatment for trastuzumab-progressed MBC. Objective response and disease control rates were 11% and 39%. The authors conclude that the clinical activity observed in this trial warrants further work with afatinib and trastuzumab combination therapy. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Afatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I clinical trial, ERBB2 (HER2)-positive breast cancer patients treated with Gilotrif (afatinib), in combination with Herceptin (trastuzumab), demonstrated an overall objective response rate of 11% (2/18) while 28% (5/18) attained a best response of stable disease. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Buparlisib (BKM-120), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I clinical trial, the combination of Buparlisib (BKM120) and Herceptin (trastuzumab) was well tolerated in patients with ERBB2 (HER2)-positive advanced or metastatic breast cancer that had progressed on Herceptin (trastuzumab). |
| ERBB2 AMPLIFICATION |
ERBB2 |
CDX-3379, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Herceptin (trastuzumab) and CDX-3379 (KTN3379) inhibited tumor growth in xenograft models of ERBB2 (HER2)-amplified breast cancer, with increased efficacy compared to KTN3379 alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Capecitabine, Cetuximab, Oxaliplatin | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
141 patients were analyzed for ERBB2 (HER2) positivity by FISH and/or IHC. Only 6 (4.3%) were ERBB2 positive. These patients did not show a difference in outcome after capecitabine, oxaliplatin and chemoradiotherapy, with or without cetuximab. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Capecitabine, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In Phase II clinical trials, the combination of Xeloda (capecitabine) and Herceptin (trastuzumab) demonstrated efficacy with a manageable toxicity profile in heavily pretreated patients with ERBB2 (HER2)-positive advanced breast cancer and earlier Herceptin (trastuzumab) exposure. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Capecitabine, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this Phase III trial, trastuzumab-based treatment was assessed in women with locally advanced or metastatic HER2 positive breast cancer who had progressed on trastuzumab. Patients had 12 weeks or greater previous trastuzumab treatment with time since end of last cycle less than 6 weeks. Primary endpoint was time to progression. 78 patients were assigned to each group, with median time to progression of 5.6 months in capecitabine group and 8.2 months in trastuzumab plus capecitabine group. The results are in contrast to the principle of change of treatment on disease progression, and authors suggest that chemotherapy-sensitizing mechanisms of trastuzumab remain intact in HER2 breast cancer cells with trastuzumab progression. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Capecitabine, Trastuzumab, Tucatinib (ARRY-380) | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib trial, the combination of Tucatinib (ARRY-380), Herceptin (trastuzumab), and Capecitabine demonstrated clinical activity in CNS metastases in patients with ERBB2 (HER2)-positive metastatic breast cancer, with 50% (1/2) of evaluable patients achieving CNS partial response and 50% (1/2) achieving CNS stable disease (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-19). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Carboplatin, Docetaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) plus Perjeta (pertuzumab) therapy, is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Carboplatin, Docetaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) therapy is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
We identified 142 patients with metastatic colorectal cancer whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF. All patients received cetuximab after oxaliplatin, irinotecan, and fluoropyrimidine failure. HER2 status was determined using immunohistochemistry and silver in situ hybridization and correlated with cetuximab efficacy. Of 142 RAS and BRAF wild-type tumors, we observed 7 cases (4.9%) of HER2 amplification by SISH. After a median follow-up of 13.2 months (range, 1.4-78.1 months), median progression-free survival (PFS) was significantly different according to HER2 status: 3.1 months in patients with HER2 amplification compared with 5.6 months in those with non-amplified HER2 (HR = 2.73; 95% CI = 1.18-6.31; P = 0.019). Overall survival (OS) was not significantly different between groups, although there was a tendency towards shorter OS in patients with HER2-amplified tumors (HR = 0.31; 95% CI = 0.61-2.82; 10.1 vs. 13.5 months; P = 0.488). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed resistance whereas 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. Among 11 quadruple-negative samples with resistance to cetuximab, HER2 overexpression and amplification (N=3) and amplification (N=1) were identified. In an independent second retrospective cohort, 3 out of 17 patients with KRAS wt, cetuximab resitant CRC were found to harbor HER2 overexpression and amplification. In this cohort no HER2 overexpression or amplification was identified in 14 KRAS wt patients with response to cetuximab. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed a response to cetuximab whereas 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. Among 11 quadruple-negative samples with resistance to cetuximab, HER2 overexpression and amplification (N=3) and amplification (N=1) were identified. In an independent second retrospective patient cohort, 3 out of 17 patients with KRAS wt, cetuximab resitant CRC were found to harbor HER2 overexpression and amplification. In this cohort no HER2 overexpression or amplification was identified in 14 KRAS wt patients with response to cetuximab. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, ERBB2 (HER2) amplification was associated with resistance to Erbitux (cetuximab) in colorectal cancer patients. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab, Lapatinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Tykerb (lapatinib) induced tumor regression in patient-derived xenograft (PDX) models of colorectal cancer with ERBB2 (HER2) amplification. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
HER2 amplification (FISH) was assessed in 170 KRAS wt mCRC patients treated with cetuximab or panitumumab. HER2 copy number status was significantly correlated with respoinse rate, PFS and OS. Patients with amplification in all neoplastic cells (4%) had worse outcome compared to patients without amplification (35%, intermediate outcome) or amplification in minor clones (61%, highest survival probability) |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cyclophosphamide, Doxorubicin, Paclitaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab) and Perjeta (pertuzumab), is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cyclophosphamide, Doxorubicin, Paclitaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab), is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Docetaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In a randomized phase 3 trial, HER2 positive metastatic breast cancer patients given first-line treatment of pertuzumab plus trastuzumb plus docetaxel experienced improved progression free survival (18.5 vs 12.4 months, P<0.001) and increased objective response rate (80.2% vs 69.3%, P=0.001) than the control group given placebo plus trastuzumab plus docetaxel. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Docetaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
Publications Database: JAX-CKB |
In a Phase III trial (CLEOPATRA) that supported FDA approval, treatment with Perjeta (pertuzumab), combined with Herceptin (trastuzumab) and Taxotere (docetaxel), improved median progression free survival to 18.5 months compared to 12.4 months with placebo plus Herceptin (trastuzumab) and Taxotere (docetaxel) in patients with ERBB2 (HER2)-positive metastatic breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Docetaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
CLEOPATRA (NCT00567190) was a Phase III, randomized and double-blind, placebo-controlled study of 808 patients with HER2-positive metastatic breast cancer. Patients were HER2-positive by IHC3+ or FISH, and patients who had received prior hormonal treatment or adjuvant/neo-adjuvant therapy with or without trastuzumab for longer than 12 months before randomization were also eligible. The two arms of the study were trastuzumab and docetaxel with either placebo or pertuzumab. Median PFS in the placebo arm was 12.4 months while in the petuzumab arm 18.5 months was achieved. Median OS in the control arm was 40.8 months and 56.5 months with pertuzumab. These strong results make a case for dual antibody blockade in first line treatments of HER2-positive metastatic breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Docetaxel, Pertuzumab, Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, Kadcyla (trastuzumab emtansine), Taxotere (docetaxel) and Perjeta (pertuzumab) combination treatment resulted in pathologic complete response in 60.3% (44/73) of patients with ERBB2 (HER2)-positive locally advanced breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Entinostat, Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination treatment consisted of Entinostat, Tykerb (lapatinib) and Herceptin (trastuzumab) resulted in complete response in 9% (2/22), partial response in 14% (3/22), and stable disease in 27% (6/22) of ERBB2 (HER2) positive breast cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 609)). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Everolimus, Trastuzumab, Vinorelbine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial (BOLERO-3), the combination of Afinitor (everolimus), Herceptin (trastuzumab), and Navelbine (vinorelbine) increased progression-free survival in patients with Herceptin (trastuzumab)-resistant, ERBB2 (HER2)-positive, advanced breast cancer who had prior taxane treatment. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Gimeracil (TS-1), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II clinical trial, the combination of TS-1 (S-1) and Herceptin (trastuzumab) demonstrated safety and efficacy in patients with ERBB2 (HER2)-positive metastatic breast cancer, with an overall response rate of 53.6% (15/28), and a clinical benefit rate of 75.0% (21/28). |
| ERBB2 AMPLIFICATION |
ERBB2 |
LJM716, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Herceptin (trastuzumab) and LJM716, resulting in a delay of brain lesion growth and improved survival. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In light of results showing increased PFS using mAB plus TKI in heavily pretreated patients, the efficacy of trastuzumab plus lapatinib in a neoadjuvant setting with untreated stage II or IIIA HER2 positive breast cancer was assessed. In this randomized 3 arm phase II study (CHER-LOB), patients received (A) chemotherapy plus trastuzumab, (B) chemotherapy plus lapatinib, or (C) chemotherapy plus trastuzumab and lapatinib, with pathologic complete response (pCR) as endpoint. From 121 patients, pCR rates were 25% in arm A, 26.3% in arm B, and 46.7% in arm C. The authors conclude these results support the superiority of dual-HER2 inhibition in the neoadjuvant context of HER2 positive BC. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
This Phase III trial compared the activity of lapatinib vs. trastuzumab vs. sequential trastuzumab followed by lapatinib vs. lapatinib plus trastuzumab in an adjuvant treatment setting. 8381 women were randomized to one of four treatment arms. Patients had HER2 positive non-metastatic operable BC. The primary endpoint was disease free survival. First results report that after median 4.5 year follow up, a non significant 16% improvement in DFS was seen in trastuzumab + lapatinib vs. trastuzumab alone. The results are interpreted as showing no added benefit for labatinib addition to trastuzumab in the adjuvant treatment context. This trial is ongoing but not recruiting patients (NCT00490139). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
This Phase III study (EGF104900) was motivated by preclinical and other data demonstrating synergistic activity between lapatinib and trastuzumab against HER2 positive breast cancer (BC) cells. In this study of HER2 positive metastatic BC which had progressed on trastuzumab, two arms were compared: lapatinib vs. lapatinib + trastuzumab. Progression free survival (PFS) was the primary endpoint. For 296 patients, 148 in each arm, median PFS of 8.1 weeks for lapatinib and 12.0 for combination therapy was observed (P=0.008). The authors conclude that in the context of metastatic trastuzumab-progressed HER2 positive BC, trastuzumab with lapatinib TKI addition is a favorable treatment. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In a randomized open label phase 3 study (NCT00553358), women with HER2 positive primary breast cancer treated with lapatinib plus trasuzumab had higher rates of pathological complete responses than seen in control groups receiving either IV trastuzumab or oral lapatinib alone (combination treatment pCR rate of 51% vs 29.5% and 24.7% for trastuzumab and lapatinib alone, respectively). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial, Tykerb (lapatinib) and Herceptin (trastuzumab) combination treatment resulted in complete response in the breast in 10.6% (7/66) and minimal residual disease in 16.7% (11/66) of ERBB2-positive breast cancer patients 11 days after receiving the treatment (European Breast Cancer Conference; Mar 2016; Abstract #6LBA). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a meta-analysis of six randomized clinical trials, Tykerb (lapatinib) and Herceptin (trastuzumab) combination treatment resulted in 13% absolute improvement in pathologic complete response rate in ERBB2 (HER2)-positive breast cancer patients compared to Herceptin (trastuzumab) single treatment. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: CIViC |
In-vitro studies using ERBB2 over-expressing breast cancer cell lines BT474 and SKBR3 (with ERBB2 amplification) showed apoptosis under either labatinib or trastuzumab treatment. A marked synergistic apoptotic effect under lapatinib and trastuzumab co-treatment was observed in BT474 cells, and a milder synergistic effect was observed in SKBR3 cells. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Neratinib, Pertuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Perjeta (pertuzumab) and Nerlynx (neratinib), resulting in a delay of brain lesion growth and improved survival. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Oxaliplatin, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Herceptin (trastuzumab) and Eloxatin (oxaliplatin) resulted in growth inhibition of ERBB2 (HER2)-positive breast cancer cells in culture. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Paclitaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Perjeta (pertuzumab), Herceptin (trastuzumab), and Taxol (paclitaxel) therapy is included in the guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-negative, ERBB2 (HER2) receptor-positive breast cancer (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Palbociclib (PD0332991), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In a panel of 47 breast cancer cell lines, HER2 overexpressing cells were among those more sensitive to CDK4/6 inhibitor Palbociclib (PD0332991). In the trastuzumab sensitive cell line Bt474, palbociclib synergized with trastuzumab in growth inhibition, while in 2 trastuzumab resistant cell lines, addition of trastuzumab to palbociclib treatment resulted in increased growth inhibition over palbociclib alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Palbociclib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Ibrance (palbociclib) and Herceptin (trastuzumab) worked synergistically to inhibit growth of ERBB2 (HER2)-amplified breast cancer cells in culture. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Pertuzumab | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 AMPLIFICATION |
ERBB2 |
Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, adjuvant Herceptin (trastuzumab), Perjeta (pertuzumab), plus chemotherapy resulted in improved invasive disease-free survival compared to Herceptin (trastuzumab) plus chemotherapy in patients with Erbb2 (Her2)-positive breast cancer (J Clin Oncol 35, 2017 (suppl; abstr LBA500)). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Pertuzumab, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Herceptin (trastuzumab) and Perjeta (pertuzumab), resulting in a delay of brain lesion growth and improved survival. |
| ERBB2 AMPLIFICATION |
ERBB2 |
S63845, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, S63845 and Herceptin (trastuzumab) demonstrated synergy in ERBB2 (HER2)-amplified breast cancer cells in culture and in ERBB2 (HER2)-amplified breast cancer patient-derived xenograft (PDX) models, resulting in enhanced tumor growth inhibition and overall survival compared to either agent alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
S63845, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, S63845 and Herceptin (trastuzumab) demonstrated synergy in ERBB2 (HER2)-amplified breast cancer cells in culture and in ERBB2 (HER2)-amplified breast cancer patient-derived xenograft (PDX) models, resulting in enhanced tumor growth inhibition and overall survival compared to either agent alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Sunitinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial, Sutent (sunitinib), in combination with Herceptin (trastuzumab), demonstrated safety and efficacy in ERBB2 (HER2) positive advanced breast cancer patients. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Tanespimycin, Trastuzumab | Breast Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
Publications Database: CIViC |
HERA was a Phase III trial assessing application of trastuzumab in an extended adjuvant setting. Patients were HER2 positive with completely excised invasive BC, node positive or negative, and having undergone prior adjuvant or neo-adjuvant chemotherapy. In the 3 arm study patients were given trastuzumab courses of 1 year, 2 years, or untreated. At the first planned interim analysis, trastuzumab treatment for one year was compared with observation alone. A significant difference in disease-free survival was seen with 220 DFS events out of 1693 in the observation arm versus 127 DFS events out of 1694 in the 1 year trastuzumab arm. 1 year adjuvant trastuzumab is currently the standard of care. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
A randomized clinical trial of 469 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved time to disease progression, objective response rate, and duration of response for patients who received trastuzumab in addition to chemotherapy compared to chemotherapy alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a meta-analysis, breast cancer patients with >12 copies of ERBB2 (HER2) had a better response to Herceptin (trastuzumab) than patients with 6-12 copies of ERBB2 (HER2). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
A randomized clinical trial of 186 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved overall survival, response rate, response duration, time to progression, and time to treatment failure for patients who received trastuzumab in addition to chemotherapy (docetaxel) compared to chemotherapy alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
Publications Database: JAX-CKB |
In a Phase III trial (EMILIA) that supported FDA approval, treatment with Kadclya (trastuzumab emtansine) improved median progression free survival (9.6 mo vs 6.4 mo) and overall survival (30.9 mo vs 25.1 mo) compared to Tykerb (lapatinib) combined with Xeloda (capecitabine) in patients with metastatic ERBB2 (HER2)-positive breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In the single arm Phase II study (TDM4258g) breast cancer patients who had progressed on previous anti-HER2 therapy were given transtuzumab emtansine (T-DM1), a HER2 monoclonal antibody and antimicrotubule drug conjugate. 95 trial participants with archival primary tumor were reassessed for HER2 status (positivity defined by FISH or IHC 3+), and 74 patients were confirmed for HER2 positivity and 21 were normal. Overall response rate was 33.8% (95% CI, 23.2% to 44.9%) in patients with confirmed HER2-positive tumors and 4.8% (95% CI, 1.0% to 21.8%) in HER2 normal patients. Median PFS was 8.2 months (95% CI, 4.4 months to not estimable) in patients with confirmed HER2-positive tumors and 2.6 months (95% CI, 1.4 to 3.9 months) in HER2 normal patients. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In a randomized phase II study, first line treatment of HER2-positive metastatic breast cancer with trastuzumab emtansine (T-DM1) resulted in improved progression free survival and fewer serious adverse effects when compared to treatment with combination trastuzumab plus docetaxel (HT) (median follow up 14 months, median PFS with T-DM1 14.2 vs 9.2 with HT). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Kadclya (trastuzumab emtansine) demonstrated improved median progression free survival and overall survival compared to Tykerb (lapatinib) and Xeloda (capecitabine) combination treatment in patients with ERBB2 (HER2) positive breast cancer, regardless of the expression level of Erbb2 (Her2), Egfr, and Her3, or PIK3CA mutation status. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
The Phase III trial, TH3RESA (NCT01419197), was performed in patients with advanced HER2 breast cancer that was heavily pretreated. Patients were required to have prior exposure to trastuzumab and lapatinib as well as a taxane. This patient population has not seen many studies, responds poorly to late-line treatment with trastuzumab, and in this study was treated with trastuzumab emtansine (T-DM1, n=404) vs. physician's choice (usually trastuzumab plus chemotherapy, n=198). Results showed progression free survival was 6.2 months in T-DM1 treatment vs. 3.3 months under physician's choice, along with lower incidence of grade 3 or worse events with T-DM1. The authors conclude that their findings in this heavily pretreated population, along with findings in the EMILIA trial, indicate promise for antibody-drug conjugates. The NCI-MATCH trial with further study T-DM1 in the context of HER2 amplification. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
Publications Database: JAX-CKB |
In a Phase III trial (EMILIA) that supported FDA approval, treatment with Kadclya (trastuzumab emtansine) improved median progression free survival (9.6 mo vs 6.4 mo) and overall survival (30.9 mo vs 25.1 mo) compared to Tykerb (lapatinib) combined with Xeloda (capecitabine) in patients with metastatic ERBB2 (HER2)-positive breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
The EMILIA study (NCT00829166) was a Phase II trial to assess the efficacy of trastuzumab emtansine (T-DM1, n=495) in comparison to lapatinib plus capecitabine (n=496), in treatment of advanced HER2 positive breast cancer. Patients were required to have progressed on or after treatments involving trastuzumab and a taxane, and no prior exposure to lapatinib or T-DM1. Primary endpoints included independently assessed progression free survival (PFS) and safety. PFS was 9.6 months in T-DM1 group vs. 6.4 months in lapatinib plus capecitabine. Rates of adverse events of grade 3 or higher were greater with lapatinib plus capecitabine. These results, together with other trials such as TH3RESA indicate promise for T-DM1 therapy in HER2 amplification, and this will be further studied in an arm of the NCI-MATCH trial. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab, Tucatinib (ARRY-380) | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib clinical trial, the combination of Tucatinib (ARRY-380) and Herceptin (trastuzumab) demonstrated clinical activity in central nervous system (CNS) metastases in patients with ERBB2 (HER2)-positive metastatic breast cancer, with 100% (3/3) patients achieving CNS stable disease as best response (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-19). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab, XL147 (Pilaralisib) | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In 5 trastuzumab resistant HER2 overexpressing breast cancer cell lines, combination of the pan-PI3K inhibitor XL147 and trastuzumab treatment induced cell death to similar or greater levels than XL147 alone. In three trastuzumab resistant cell lines tested, colony formation in matrigel was markedly inhibited by combination treatment. Apoptotic markers were apparent with combination treatment. In athymic mice, trastuzumab resistant cell line HR6 was used in tumor xenografts and tumors were allowed to form. Mice subsequently treated with trastuzumab or XL147 showed continued tumor growth without marked difference from control, while combination treatment essentially halted tumor growth rate. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Tucatinib (ARRY-380), Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib clinical trial, treatment with the combination of Tucatinib (ARRY-380) and Trastuzumab emtansine (T-DM1) resulted in an overall response rate of 47% (15/52) and median progression-free survival of 6.5 months in patients with ERBB2 (HER2)-positive metastatic breast cancer, including patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 513)). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Tucatinib (ARRY-380), Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib clinical trial, treatment with the combination of Tucatinib (ARRY-380) and Trastuzumab emtansine (T-DM1) resulted in partial response in 33% (11/33) and stable disease in 48% (16/33) and a clinical benefit rate of 58% (19/33) in patients with ERBB2 (HER2)-positive metastatic breast cancer (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-20). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Tucatinib (ARRY-380), Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib trial, the combination of Tucatinib (ARRY-380) and Trastuzumab emtansine (T-DM1) demonstrated clinical activity in CNS metastases in patients with ERBB2 (HER2)-positive metastatic breast cancer, with 12.5% (1/8) evaluable patients achieving CNS complete response, 25% (2/8) partial CNS response, and 62.5% (5/8) CNS stable disease (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-19). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Vinorelbine or Paclitaxel, Everolimus, Trastuzumab | Breast Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer.// Everolimus combined with weekly paclitaxel and trastuzumab was generally well tolerated and had encouraging antitumor activity in patients with trastuzumab-pretreated and -resistant metastatic HER2-overexpressing breast cancer. |
| ERBB2 AMPLIFICATION, ERBB2 L755S |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, expression of ERBB2 (HER2) L755S conferred resistance to Tykerb (lapatinib) plus Herceptin (trastuzumab) combination therapy in ESR1-positive/ERBB2 (HER2)-positive breast cancer cells with ERBB2 amplification in culture. |
| ERBB2 AMPLIFICATION, ERBB2 L755S |
ERBB2 |
Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, expression of ERBB2 (HER2) L755S conferred resistance to Perjeta (pertuzumab) plus Herceptin (trastuzumab) combination therapy in ESR1-positive/ERBB2 (HER2)-positive breast cancer cells with ERBB2 amplification in culture. |
| ERBB2 AMPLIFICATION, ERBB2 L755S |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, expression of ERBB2 (HER2) L755S resulted in decreased sensitivity to treatment with Kadcyla (trastuzumab emtansine) in ESR1-positive/ERBB2 (HER2)-positive breast cancer cells with ERBB2 amplification in culture. |
| ERBB2 AMPLIFICATION, ERBB2 L866M |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, xenograft models of patient derived colorectal cancer cells harboring ERBB2 (HER2) L866M and ERBB2 (HER2) amplification were resistant to Erbitux (cetuximab). |
| ERBB2 AMPLIFICATION, ERBB2 T798M |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a human ERBB2-amplified breast cancer cell line expressing ERBB2 (HER2) T798M was resistant to Herceptin (trastuzumab) in culture and in xenograft models. |
| ERBB2 AMPLIFICATION, ERBB3 OVEREXPRESSION |
ERBB2 ERBB3 |
Buparlisib (BKM-120), Pertuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a breast cancer cell line xenograft model harboring ERBB2 (HER2) amplification and ERBB3 (HER3) over expression in brain metastases was sensitive to the combined treatment of Buparlisib (BKM120) and Perjeta (pertuzumab), demonstrating delayed tumor growth and better survival when compared to either treatment alone. |
| ERBB2 AMPLIFICATION, ERBB3 OVEREXPRESSION, PIK3CA E545K |
ERBB2 ERBB3 PIK3CA |
Buparlisib (BKM-120), Pertuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a breast cancer cell line xenograft model harboring ERBB2 (HER2) amplification, ERBB3 (HER3) over expression, and PIK3CA E545K in brain metastases was sensitive to the combined treatment of Buparlisib (BKM120) and Perjeta (pertuzumab), demonstrating delayed tumor growth and better survival when compared to either treatment alone. |
| ERBB2 AMPLIFICATION, FGF19 AMPLIFICATION, FGF3 AMPLIFICATION, FGF4 AMPLIFICATION |
ERBB2 FGF19 FGF3 FGF4 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, amplification of FGF3, FGF4, and FGF19 was associated with acquired resistance to combination treatment with Herceptin (trastuzumab) and Tykerb (lapatinib) in an ERBB2 (HER2)-amplified breast cancer cell line xenograft model. |
| ERBB2 AMPLIFICATION, HGF AMPLIFICATION |
ERBB2 HGF |
Trastuzumab | Breast Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Increased MET and HGF gene copy numbers are associated with trastuzumab failure in HER2-positive metastatic breast cancer. |
| ERBB2 AMPLIFICATION, IL6 OVEREXPRESSION, IL6R OVEREXPRESSION, PTEN DELETION |
ERBB2 IL6 IL6R PTEN |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a human breast cancer cell line with amplification of Erbb2, loss of Pten and autocrine IL6 signaling was resistant to Herceptin (trastuzumab) in culture and in xenograft models. |
| ERBB2 AMPLIFICATION, MET AMPLIFICATION |
ERBB2 MET |
Trastuzumab | Breast Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Increased MET and HGF gene copy numbers are associated with trastuzumab failure in HER2-positive metastatic breast cancer. |
| ERBB2 AMPLIFICATION, MET AMPLIFICATION |
ERBB2 MET |
Trastuzumab | Breast Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
High GCNs of MET and HGF associate with an increased risk of trastuzumab-based therapy failure in HER2-positive MBC.// Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer. |
| ERBB2 AMPLIFICATION, MUC4 OVEREXPRESSION |
ERBB2 MUC4 |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, ERBB2-amplified breast cancer cells that overexpressed MUC4 were resistant to Herceptin (trastuzumab) in cell culture. |
| ERBB2 AMPLIFICATION, PIK3CA ACTIVATING MUTATION |
ERBB2 PIK3CA |
Buparlisib (BKM-120), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, the combination of Buparlisib (BKM120) and Herceptin (trastuzumab) was well tolerated and resulted in some preliminary efficacy in patients with ERBB2 (HER2)-positive breast cancer harboring PIK3CA activating mutations and/or PTEN mutations that had progressed on trastuzumab-based therapy. |
| ERBB2 AMPLIFICATION, PIK3CA ACTIVATING MUTATION |
ERBB2 PIK3CA |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis, ERBB2 (HER2)-positive breast cancer patients with PI3K pathway activation due to PTEN loss and/or PIK3CA activating mutation demonstrated a decreased median progression-free survival of 4.5 months, compared to 9.0 months for patients without PI3K pathway activation following treatment with a Herceptin (trastuzumab) containing regimen. |
| ERBB2 AMPLIFICATION, PIK3CA ACTIVATING MUTATION |
ERBB2 PIK3CA |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, ERBB2 (HER2)-positive breast cancer patients with PI3K pathway activation resulting from low PTEN expression and/or PIK3CA activating mutations demonstrated decreased progression-free survival following treatment with Herceptin (trastuzumab) compared to patients without PI3K pathway activation. |
| ERBB2 AMPLIFICATION, PIK3CA C420R |
ERBB2 PIK3CA |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA C420R in culture. |
| ERBB2 AMPLIFICATION, PIK3CA E545K |
ERBB2 PIK3CA |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of Herceptin (trastuzumab)-resistant ERBB2 (HER2) positive breast cancer cells harboring PIK3CA E545K in culture, and induced tumor regression in cell line xenograft models. |
| ERBB2 AMPLIFICATION, PIK3CA H1047R |
ERBB2 PIK3CA |
CH-5132799, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of CH5132799 and Herceptin (trastuzumab) inhibited tumor growth and overcame Herceptin (trastuzumab) insensitivity in xenograft models of a human breast cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification. |
| ERBB2 AMPLIFICATION, PIK3CA H1047R |
ERBB2 PIK3CA |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of Herceptin (trastuzumab)-resistant ERBB2 (HER2) positive breast cancer cells harboring PIK3CA H1047R in culture, and induced tumor regression in cell line xenograft models. |
| ERBB2 AMPLIFICATION, PIK3CA I391M |
ERBB2 PIK3CA |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA K111N in culture. |
| ERBB2 AMPLIFICATION, PIK3CA K111N |
ERBB2 PIK3CA |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA K111N in culture, and induced tumor regression in cell line xenograft models. |
| ERBB2 AMPLIFICATION, PIK3CA MUTATION |
ERBB2 PIK3CA |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a retrospective analysis of the combined treatment, Herceptin (trastuzumab) and Tykerb (lapatinib), in ERBB2 (HER2) positive breast cancer patients demonstrated patients harboring a PIK3CA mutation trended towards a decreased response when compared to patients with wild-type PIK3CA. |
| ERBB2 AMPLIFICATION, PIK3CA MUTATION |
ERBB2 PIK3CA |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a retrospective analysis of Herceptin (trastuzumab) treatment in ERBB2 (HER2) positive breast cancer patients demonstrated patients harboring a PIK3CA mutation trended towards a decreased response when compared to patients with wild-type PIK3CA. |
| ERBB2 AMPLIFICATION, PIK3CA ONCOGENIC MUTATION |
ERBB2 PIK3CA |
Vinorelbine or Paclitaxel, Everolimus, Trastuzumab | Breast Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3. |
| ERBB2 AMPLIFICATION, PTEN DELETION |
ERBB2 PTEN |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis, ERBB2 (HER2)-positive breast cancer patients with PTEN loss demonstrated a decreased median progression-free survival of 6.0 months, compared to 9.0 months for patients without PI3K pathway activation following treatment with a Herceptin (trastuzumab) containing regimen. |
| ERBB2 AMPLIFICATION, PTEN MUTATION |
ERBB2 PTEN |
Buparlisib (BKM-120), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I clinical trial, the combination of Buparlisib (BKM120) and Herceptin (trastuzumab) was well tolerated and resulted in some preliminary efficacy in patients with ERBB2 (HER2)-positive breast cancer harboring PIK3CA activating mutations and/or PTEN mutations that had progressed on Herceptin (trastuzumab)-based therapy. |
| ERBB2 AMPLIFICATION, PTEN ONCOGENIC MUTATION |
ERBB2 PTEN |
Vinorelbine or Paclitaxel, Everolimus, Trastuzumab | Breast Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3. |
| ERBB2 AMPLIFICATION, PTEN UNDEREXPRESSION |
ERBB2 PTEN |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, ERBB2 (HER2)-positive breast cancer patients with PI3K pathway activation resulting from low PTEN expression and/or PIK3CA activating mutations demonstrated decreased progression-free survival following treatment with Herceptin (trastuzumab) compared to patients without PI3K pathway activation. |
| ERBB2 AMPLIFICATION, RARA AMPLIFICATION |
ERBB2 RARA |
Trastuzumab, Tretinoin | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Vesanoid (tretinoin) and Herceptin (trastuzumab) resulted in an additive therapeutic effect when treating breast cancer cells harboring a co-amplification of ERBB2 (HER2) and RARA. |
| ERBB2 C311R |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Preclinical |
Publications Database: CGI |
Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. |
| ERBB2 D769H |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Preclinical |
Publications Database: CGI |
Activating HER2 mutations in HER2 gene amplification negative breast cancer. |
| ERBB2 D769H |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cell lines expressing ERBB2 D769H reverted to normal morphology in culture upon Herceptin (trastuzumab) treatment. |
| ERBB2 D769Y |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Preclinical |
Publications Database: CGI |
Activating HER2 mutations in HER2 gene amplification negative breast cancer. |
| ERBB2 D769Y |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cell lines expressing ERBB2 D769Y reverted to normal morphology in culture upon Herceptin (trastuzumab) treatment. |
| ERBB2 G309A |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cell lines expressing ERBB2 G309A reverted to normal morphology in culture upon Herceptin (trastuzumab) treatment. |
| ERBB2 G309E |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Preclinical |
Publications Database: CGI |
Activating HER2 mutations in HER2 gene amplification negative breast cancer.// Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. |
| ERBB2 G778_P780dup MUTATION |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cell lines expressing ERBB2 P780_Y781insGSP demonstrated resistance when treated with Herceptin (trastuzumab). |
| ERBB2 I655V |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer. HER2 Ile655Val polymorphism affects the function of HER2 gene only restricted in HER2-positive breast cancers. HER2-positive breast cancer patients with the Val variant have an aggressive phenotype, but are sensitive to trastuzumab treatment. |
| ERBB2 K753E |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cells expressing ERBB2 (HER2) K753E were resistant to Herceptin (trastuzumab) in culture. |
| ERBB2 L755S |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) L755S were resistant to Erbitux (cetuximab) in culture. |
| ERBB2 L755S |
ERBB2 |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) L755S were resistant to Vectibix (panitumumab) in culture. |
| ERBB2 L755S |
ERBB2 |
Trastuzumab, Afatinib, Lapatinib, Neratinib | Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
Resistance to anti-HER2 therapies in HER2+ breast cancer can occur through activation of alternative survival pathways or reactivation of the HER signaling network. Ectopic expression of HER2 L755S induced acquired lapatinib resistance in the BT474/AZ, SK-BR-3, and AU565 parental cell lines. HER2 L755S-specific siRNA knockdown reversed the resistance in BT474/AZ-LR and BT474/ATCC-LTR lines. The HER1/2-irreversible inhibitors afatinib and neratinib substantially inhibited both resistant cell growth and the HER2 and downstream AKT/MAPK signaling driven by HER2 L755S in vitro and in vivo. HER2 reactivation through acquisition of the HER2 L755S mutation was identified as a mechanism of acquired resistance to lapatinib-containing HER2-targeted therapy in preclinical HER2-amplified breast cancer models, which can be overcome by irreversible HER1/2 inhibitors. |
| ERBB2 L768S |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cells expressing ERBB2 (HER2) L768S were sensitive to Herceptin (trastuzumab) in culture, resulting in decreased colony formation. |
| ERBB2 L866M |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) L866M were resistant to Erbitux (cetuximab) in culture. |
| ERBB2 L866M |
ERBB2 |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) L866M were resistant to Vectibix (panitumumab) in culture. |
| ERBB2 OVEREXPRESSION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, ERBB2 (HER2) over expression was associated with resistance to Erbitux (cetuximab) treatment in a human cell line xenograft model of colorectal cancer. |
| ERBB2 OVEREXPRESSION |
ERBB2 |
MM-302, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination of MM-302 and Herceptin (trastuzumab) synergistically inhibited tumor growth in cell line xenograft models of Erbb2 (Her2)-over expressing breast cancer. |
| ERBB2 OVEREXPRESSION |
ERBB2 |
Pertuzumab | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 OVEREXPRESSION |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 OVEREXPRESSION |
ERBB2 |
Trastuzumab Emtansine | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 OVEREXPRESSION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
Publications Database: JAX-CKB |
In a Phase III trial (EMILIA) that supported FDA approval, treatment with Kadclya (trastuzumab emtansine) improved median progression free survival (9.6 mo vs 6.4 mo) and overall survival (30.9 mo vs 25.1 mo) compared to Tykerb (lapatinib) combined with Xeloda (capecitabine) in patients with metastatic ERBB2 (HER2)-positive breast cancer. |
| ERBB2 OVEREXPRESSION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Trastuzumab emtansine has its indication for patients with HER2-positive metastatic breast cancer after therapy with Trastuzumab and Taxane, approval based on PFS and preliminary OS data. EMILIA was a randomised open-label, phase III study for patients with HER2-positive, unresectable, locally advanced, or metastatic breast cancer previously treated with Trastuzumab and a Taxane, randomized 1:1 to Trastuzumab-emtansine or Capecitabine plus Lapatinib. 991 patients were enrolled. Median OS was 29.9m vs. 25.9m. Fewer grade 3 or worse AE occurred with trastuzumab emtansine than with capecitabine plus lapatinib control treatment. |
| ERBB2 OVEREXPRESSION, ERBB3 OVEREXPRESSION |
ERBB2 ERBB3 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Herceptin (trastuzumab) and Tykerb (lapatinib) in ERBB2 (HER2)-receptor positive breast cancer cells resulted in decreased phosphorylation of Erbb3 (Her3) in culture and complete tumor regression in 100% (8/8) of the cell line xenograft models compared to incomplete regression when treated with either agent alone. |
| ERBB2 OVEREXPRESSION, PIK3CA H1047R |
ERBB2 PIK3CA |
Buparlisib (BKM-120), Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Buparlisib (BKM120), Herceptin (trastuzumab), and Tykerb (lapatinib) inhibited tumor growth in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R, but efficacy was not significantly improved over Buparlisib (BKM120) alone. |
| ERBB2 OVEREXPRESSION, PIK3CA H1047R |
ERBB2 PIK3CA |
Buparlisib (BKM-120), Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Buparlisib (BKM120), Herceptin (trastuzumab), and Perjeta (pertuzumab) inhibited tumor growth in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R, with improved efficacy over Buparlisib (BKM120) alone. |
| ERBB2 OVEREXPRESSION, PIK3CA H1047R |
ERBB2 PIK3CA |
Buparlisib (BKM-120), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Herceptin (trastuzumab) and Buparlisib (BKM120) inhibited tumor growth in mouse ERBB2 (HER2)-over expressing breast cancer models expressing PIK3CA H1047R, with moderate efficacy over Buparlisib (BKM120) alone. |
| ERBB2 OVEREXPRESSION, PIK3CA H1047R |
ERBB2 PIK3CA |
Lapatinib, Pertuzumab, Trastuzumab | Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In sum, PIK3CA(H1047R) accelerates HER2-mediated breast epithelial transformation and metastatic progression, alters the intrinsic phenotype of HER2-overexpressing cancers, and generates resistance to approved combinations of anti-HER2 therapies. |
| ERBB2 OVEREXPRESSION, PIK3CA H1047R |
ERBB2 PIK3CA |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a mouse breast cancer model with mammary ERBB2 (HER2) over-expression that also expressed the PIK3CA H1047R mutation showed resistance to the combination of Herceptin (trastuzumab) and Tykerb (lapatinib). |
| ERBB2 OVEREXPRESSION, PIK3CA H1047R |
ERBB2 PIK3CA |
Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a mouse breast cancer model with ERBB2 (HER2) over-expression that also expressed the PIK3CA H1047R mutation showed resistance to the combination of Heceptin (trastuzumab) and Perjeta (pertuzumab). |
| ERBB2 OVEREXPRESSION, PIK3CA H1047R |
ERBB2 PIK3CA |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, mouse breast cancer models over expressing ERBB2 (HER2) and expressing PIK3CA H1047R were resistant to Herceptin (trastuzumab). |
| ERBB2 OVEREXPRESSION, PIK3CA MUTATION |
ERBB2 PIK3CA |
ARQ092, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a breast cancer xenograft model with ERBB2 (HER2) over expression and harboring a PIK3CA mutation was sensitive to the combination treatment of ARQ092 and Herceptin (trastuzumab), demonstrating greater inhibition of tumor growth when compared to treatment with either agent alone. |
| ERBB2 OVEREXPRESSION, PIK3CA MUTATION |
ERBB2 PIK3CA |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial, ERBB2-positive breast cancer patients harboring PIK3CA mutations demonstrated lower pathologic complete remission rate (12.5%) compared to those with wild-type PIK3CA (48.4%) after Herceptin (trastuzumab) and Tykerb (lapatinib) combination therapy. |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
AC (Doxorubicin and Cyclophosphamide), Anastrozole, Paclitaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab) and Perjeta (pertuzumab), followed by Arimidex (anastrozole), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
AC (Doxorubicin and Cyclophosphamide), Letrozole, Paclitaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab) and Perjeta (pertuzumab), followed by Femara (letrozole), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
AC (Doxorubicin and Cyclophosphamide), Paclitaxel, Pertuzumab, Tamoxifen, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab) and Perjeta (pertuzumab), followed by Nolvadex (tamoxifen), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
AC (Doxorubicin and Cyclophosphamide), Paclitaxel, Pertuzumab, Trastuzumab, Exemestane | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab) and Perjeta (pertuzumab), followed by Aromasin (exemestane), is indicated in the guidelines for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Anastrozole, Carboplatin, Docetaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab), followed by Arimidex (anastrozole), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Anastrozole, Cyclophosphamide, Doxorubicin, Paclitaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab), followed by Arimidex (anastrozole) is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Carboplatin, Docetaxel, Exemestane, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) plus Perjeta (pertuzumab), followed by Aromasin (exemestane), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Carboplatin, Docetaxel, Exemestane, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab), followed by Aromasin (exemestane), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Carboplatin, Docetaxel, Letrozole, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) plus Perjeta (pertuzumab), followed by Femara (letrozole), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Carboplatin, Docetaxel, Letrozole, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab), followed by Femara (letrozole), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Carboplatin, Docetaxel, Pertuzumab, Tamoxifen, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) plus Perjeta (pertuzumab), followed by Nolvadex (tamoxifen), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Carboplatin, Docetaxel, Tamoxifen, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab), followed by Nolvadex (tamoxifen), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Cyclophosphamide, Doxorubicin, Exemestane, Paclitaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab), followed by Aromasin (exemestane), is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Cyclophosphamide, Doxorubicin, Letrozole, Paclitaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab), followed by Femara (letrozole) is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Cyclophosphamide, Doxorubicin, Paclitaxel, Tamoxifen, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab), followed by Nolvadex (tamoxifen) is included in the guidelines as adjuvant therapy for patients with hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 POSITIVE, ESR1 POSITIVE, PGR POSITIVE |
ERBB2 ESR1 PGR |
Paclitaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Perjeta (pertuzumab), Herceptin (trastuzumab), and Taxol (paclitaxel) therapy is included in the guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 R896C |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Preclinical |
Publications Database: CGI |
Activating HER2 mutations in HER2 gene amplification negative breast cancer. |
| ERBB2 R896C |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cell lines expressing ERBB2 R896C reverted to normal morphology in culture upon Herceptin (trastuzumab) treatment. |
| ERBB2 S310F |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) S310F were resistant to Erbitux (cetuximab) in culture. |
| ERBB2 S310F |
ERBB2 |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) S310F were resistant to Vectibix (panitumumab) in culture. |
| ERBB2 S310F |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Preclinical |
Publications Database: CGI |
Activating HER2 mutations in HER2 gene amplification negative breast cancer.// Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. |
| ERBB2 S310F, ESR1 OVEREXPRESSION |
ERBB2 ESR1 |
Fulvestrant, Pertuzumab, Trastuzumab | Estrogen-Receptor Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case report, treatment with Herceptin (trastuzumab) in combination with Perjeta (pertuzumab) and Fulvestrant, resulted in rapid and long-lasting (12 months) response in an ESR1-positive breast cancer patient with liver metastasis that harbored ERBB2 S310F and did not demonstrate ERBB2 (HER2) amplification. |
| ERBB2 S310Y |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, xenograft models of patient derived colorectal cancer cells harboring ERBB2 (HER2) S310Y were resistant to Erbitux (cetuximab). |
| ERBB2 S310Y |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Preclinical |
Publications Database: CGI |
Activating HER2 mutations in HER2 gene amplification negative breast cancer.// Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. |
| ERBB2 T798M |
ERBB2 |
Cetuximab, Lapatinib, Trastuzumab | Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2. Addition of the EGFR neutralizing antibody cetuximab or lapatinib restored trastuzumab sensitivity of BT474-T798M cells and xenografts, suggesting that increased EGFR ligand production was causally associated with drug resistance. |
| ERBB2 T798M |
ERBB2 |
Cetuximab, Lapatinib, Trastuzumab | Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2. Addition of the EGFR neutralizing antibody cetuximab or lapatinib restored trastuzumab sensitivity of BT474-T798M cells and xenografts, suggesting that increased EGFR ligand production was causally associated with drug resistance. |
| ERBB2 T798M |
ERBB2 |
Lapatinib, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, human breast cancer cell lines and cell line xenografts expressing ERBB2 T798M demonstrated sensitivity to the combination of Herceptin (trastuzumab) and Tykerb (lapatinib). |
| ERBB2 T798M |
ERBB2 |
Trastuzumab, XL147 | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, breast cancer cells expressing ERBB2 (HER2) T798M were sensitive to the combination of Herceptin (trastuzumab) and XL147. |
| ERBB2 V773L |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cells expressing ERBB2 (HER2) V773L were sensitive to Herceptin (trastuzumab) in culture, resulting in decreased colony formation. |
| ERBB2 V777L |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, human colorectal cancer cells over expressing ERBB2 (HER2) V777L were resistant to Erbitux (cetuximab) in culture and in patient-derived xenograft models. |
| ERBB2 V777L |
ERBB2 |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) V777L were resistant to Vectibix (panitumumab) in culture. |
| ERBB2 V777L |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cell lines expressing ERBB2 V777L reverted to normal morphology in culture upon Herceptin (trastuzumab) treatment. |
| ERBB2 V842I |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing ERBB2 (HER2) V842I were resistant to Erbitux (cetuximab) in culture. |
| ERBB2 V842I |
ERBB2 |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing ERBB2 (HER2) V842I were resistant to Vectibix (panitumumab) in culture. |
| ERBB2 V842I |
ERBB2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, transformed human breast cell lines expressing ERBB2 V842I reverted to normal morphology in culture upon Herceptin (trastuzumab) treatment. |
| ERBB3 G284R |
ERBB3 |
Lapatinib, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, the combination treatment of Herceptin (trastuzumab) and Tykerb (lapatinib) in a patient with breast cancer harboring ERBB3 (HER3) G284R resulted in antitumor efficacy, demonstrating a complete metabolic response after day 14 of treatment, a partial response after 8 weeks of treatment, and no clinical evidence of disease after 40 weeks of treatment. |
| ERBB3 OVEREXPRESSION |
ERBB3 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
High expression of ERBB3 (her3) was associated with shorter overall survival (OS) from Cetuximab treatment in patients with metastatic colorectal cancer. Gene expression measures (qRT-PCR) were available for 103 patients. |
| ERBB3 OVEREXPRESSION, PIK3CA H1047R |
ERBB3 PIK3CA |
Buparlisib (BKM-120), Pertuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a breast cancer cell line xenograft model harboring ERBB3 (HER3) over expression and PIK3CA H1047R in brain metastases was sensitive to the combined treatment of Buparlisib (BKM120) and Perjeta (pertuzumab), demonstrating delayed tumor growth and better survival when compared to either treatment alone. |
| ERBB4 NUCLEAR TRANSLOCATION |
ERBB4 |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Preclinical |
Publications Database: CIViC |
HER4 nuclear translocation was identified as a mediator of trastuzumab resistance in HER2 positive breast cancer cell lines. Increased nuclear staining was also identified in xenograft and patient samples after trastuzumab treatment. |
| ERBB4 UNDEREXPRESSION |
ERBB4 |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Preclinical |
Publications Database: CIViC |
siRNA knockdown of HER4 or inhibition with neratinib enhanced trastuzumab response in breast cancer cell lines. |
| EREG OVEREXPRESSION |
EREG |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
226 cetuximab-treated patients with CRC were analyzed for mRNA expression of EGFR and its ligands. Favorable predictors in a multivariate analysis were high AREG mRNA in KRAS wild type tumours, high EREG mRNA and low Ephrin A2 receptor mRNA. |
| EREG OVEREXPRESSION |
EREG |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Prospectively planned retrospective biomarker study in archived tumor tissue from 323 patients from the PICCOLO trial (panitumumab plus irinotecan in CRC patients with KRAS wt). Tumors were classified as high expressor (either EREG or AREG mRNA level) or low expressor (neither EREG nor AREG in top tertile). For RAS wild-type patients with high ligand expression, median PFS was 8.3 [4.0-11.0] months (irinotecan with panitumumab) vs 4.4 [2.8-6.7] months (irinotecan alone); HR, 0.38 [95% CI, 0.24-0.61]; P < .001. In RAS wild-type patients with low ligand expression, median PFS was 3.2 [2.7-8.1] months (irinotecan with panitumumab) vs 4.0 [2.7-7.5] months (irinotecan); HR, 0.93 [95% CI, 0.64-1.37]; P = .73; interaction test results were significant [P = .01]). Results were less clear for response rate (interaction P = .17) and OS (interaction P = .11). |
| FBXW7 MUTATION |
FBXW7 |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
65 patients were retrospectively analyzed for mutational profiles predictive of response to EGFR-inhibitors (cetuximab or panitumumab). FBXW7 mutation was found to be more prevalent in non-responders (5 mutations) than responders (1 mutation). |
| GNAS R201C |
GNAS |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Phase 1b study of vemurafenib, cetuximab and irinotecan in 19 BRAF V600E mutant colorectal cancer patients. cfDNA panel sequencing was performed in 10 patients after disease progression. One patient acquired a novel GNAS1 R201C mutation at disease progression. |
| HGF OVEREXPRESSION |
HGF |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, over expression of HGF conferred resistance to Erbitux (cetuximab) in colorectal cancer cell lines in culture and in xenograft models. |
| HGF OVEREXPRESSION |
HGF |
Cetuximab, JNJ-38877605 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of JNJ-38877605 and Erbitux (cetuximab) inhibited growth of colorectal cancer cell lines over expressing HGF in culture, and induced tumor regression in xenograft models. |
| HGF OVEREXPRESSION |
HGF |
JNJ-38877605, Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of JNJ-38877605 and Vectibix (panitumumab) inhibited growth of colorectal cancer cell lines over expressing HGF in culture. |
| HGF OVEREXPRESSION |
HGF |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, over expression of HGF conferred resistance to Vectibix (panitumumab) in colorectal cancer cell lines in culture. |
| HRAS G13D |
HRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
In an in vitro study, Colo-320, SW48, and CaCO2 cell lines expressing HRAS G13D mutation were associated with resistance to cetuximab treatment, as compared to Colo-320, SW48, and CaCO2 cells expressing wild-type HRAS. |
| KRAS 117 |
KRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| KRAS 12 |
KRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| KRAS 12 |
KRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| KRAS 13 |
KRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| KRAS 13 |
KRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| KRAS 146 |
KRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| KRAS 59 |
KRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| KRAS 61 |
KRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| KRAS A146P |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In irinotecan-resistant metastatic colorectal cancer patients who had been treated with cetuximab and irinotecan, KRAS mutations in codon 61 or 146 were associated with shorter progression-free survival compared to wildtype KRAS (3.8mo vs. 5.1mo, HR:0.46, 95% CI:0.11-0.88, P=0.028). In BRAF wildtype patients, KRAS mutations in codon 61 or 146 were associated with reduced response rate (0% vs. 37%, P=0.047) and reduced progression-free survival compared to wildtype KRAS patients (3.8mo vs. 5.3mo, HR:0.45, 95% CI:0.10-0.85, P=0.023). |
| KRAS A146T |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a colorectal cancer cell line harboring KRAS A146T demonstrated resistance to tumor growth inhibition by Erbitux (cetuximab) in xenograft models. |
| KRAS A146T |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
Preclinical data supporting resistance of Exon 4 mutations, in particular A146T, to cetuximab and sensitivity to PD0325901. This study involved treatment of mice bearing A146T KRAS xenografts treated with PD0325901 or cetuximab. |
| KRAS A146T |
KRAS |
Cetuximab, FOLFOX | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 148 treatment naive metastatic colorectal cancer patients, patients with RAS mutations and wildtype BRAF (n=10), including A146T (N=3), G15D (N=1), and V152M/NRAS V160A, treated with FOLFOX4 plus cetuximab were associated with decreased overall survival (16.3mo vs. 28.5mo, HR:0.43, 95% CI:0.20-0.89, P=0.020) and decreased progression free survival (7.2mo vs. 9.7mo, HR:0.56, 95% CI:0.27-1.16, P=0.11), as compared to patients with wild-type KRAS, NRAS and BRAF. |
| KRAS A59T |
KRAS |
FOLFIRI Regimen, Panitumumab | Colon Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that KRAS-mutated metastatic colorectal cancers do not respond effectively to inhibition of epidermal growth factor receptor (EGFR) with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. This report describes a case of a patient with metastatic colon cancer harboring the p.A59T variant of KRAS, with objective radiographic response (36% decrease per RECIST 1.1) and carcinoembryonic antigen biomarker response to panitumumab therapy given with FOLFIRI chemotherapy. We propose that A59T represents one potential exception to the guidelines that KRAS mutant tumors fail to respond to therapy with EGFR inhibitors, altering the paradigm of using this generalized approach. |
| KRAS A59T |
KRAS |
FOLFIRI Regimen, Panitumumab | Malignant Colon Neoplasm | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, a colon cancer patient harboring KRAS A59T demonstrated sensitivity to the combination treatment of Vectibix (panitumumab) and FOLFIRI, which resulted in an objective response of a 36% decrease according to RECIST. |
| KRAS EXON 2 |
KRAS |
Cetuximab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Erbitux (cetuximab) is not indicated for use in colon cancer patients with KRAS exon 2 mutations (NCCN.org). |
| KRAS EXON 2 |
KRAS |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, the combination of Erbitux (cetuximab) and Selumetinib (AZD6244) demonstrated safety, but minimal efficacy, in patients with metastatic colorectal cancer harboring KRAS exon 2 mutations, with no responses and 36% (5/14) of patients achieving stable disease. |
| KRAS EXON 2 |
KRAS |
Panitumumab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Vectibix (panitumumab) is not indicated for use in colon cancer patients with KRAS exon 2 mutations (NCCN.org). |
| KRAS EXON 2 MUTATION |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Guidelines |
Publications Database: CIViC |
KRAS mutation status was assessed in 394 tumor samples from colorectal cancer patients who were randomly assigned to receive cetuximab plus best supportive care or best supportive care alone. 42% of the tumors evaluated had at least one mutation in exon 2. Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab. The effectiveness of cetuximab was significantly associated with K-ras mutation status (P=0.01 for overall survival and P<0.001 for progression-free survival). In patients with wild-type K-ras tumors, treatment with cetuximab as compared with supportive care alone significantly improved overall survival. The related clinical trial ID is NCT00079066. |
| KRAS EXON 2 MUTATION |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Patients with colorectal cancer who harbor KRAS mutation have low response rate to cetuximab. |
| KRAS EXON 3 |
KRAS |
Cetuximab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Erbitux (cetuximab) is not indicated for use in colon cancer patients with KRAS exon 3 mutations (NCCN.org). |
| KRAS EXON 3 |
KRAS |
Panitumumab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Vectibix (panitumumab) is not indicated for use in colon cancer patients with KRAS exon 3 mutations (NCCN.org). |
| KRAS EXON 4 |
KRAS |
Cetuximab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Erbitux (cetuximab) is not indicated for use in colon cancer patients with KRAS exon 4 mutation (NCCN.org). |
| KRAS EXON 4 |
KRAS |
Panitumumab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Vectibix (panitumumab) is not indicated for use in colon cancer patients with KRAS exon 4 mutations (NCCN.org). |
| KRAS G12/G13 |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Chemotherapy-refractory patients with colorectal cancer harboring KRAS mutations (primarily G12/G13) had lower response and disease control rates and shorter progression free and overall survival following cetuximab plus chemotherapy than those with wildtype KRAS. |
| KRAS G12/G13 |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
KRAS mutations were significantly associated with lack of response to cetuximab in patients with advanced colorectal cancer. |
| KRAS G12A |
KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) inhibited growth of human colorectal cancer cells harboring KRAS G12A in culture. |
| KRAS G12A |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced response to panitumumab compared to wildtype KRAS (HR:0.99, 95% CI:0.73-1.36 vs. HR:0.45, 95% CI:0.34-0.59; P<0.0001). Additionally, patients with KRAS mutations showed no significant improvement between treatment with panitumumab and best supportive care alone (PFS: 7.4 wk vs 7.3 wk). |
| KRAS G12C |
KRAS |
Cetuximab, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring KRAS G12C in culture. |
| KRAS G12C |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced response to panitumumab compared to wildtype KRAS (HR:0.99, 95% CI:0.73-1.36 vs. HR:0.45, 95% CI:0.34-0.59; P<0.0001). Additionally, patients with KRAS mutations showed no significant improvement between treatment with panitumumab and best supportive care alone (PFS: 7.4 wk vs 7.3 wk). |
| KRAS G12D |
KRAS |
Cetuximab, LSN3074753 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in patient-derived xenograft models of colorectal cancer harboring KRAS G12D. |
| KRAS G12D |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced response to panitumumab compared to wildtype KRAS (HR:0.99, 95% CI:0.73-1.36 vs. HR:0.45, 95% CI:0.34-0.59; P<0.0001). Additionally, patients with KRAS mutations showed no significant improvement between treatment with panitumumab and best supportive care alone (PFS: 7.4 wk vs 7.3 wk). |
| KRAS G12D, PIK3CA Q546R |
KRAS PIK3CA |
Bevacizumab, Sorafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, a patient with colorectal cancer harboring KRAS G12D and PIK3CA Q546R demonstrated sensitivity to treatment with the combination of Nexavar (sorafenib) and Avastin (bevacizumab), resulting in stable disease for more than 6 months. |
| KRAS G12R |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
In an in vitro study to identify cetuximab-resistant clones following continuous drug treatment, a resistant clone of the Lim1215 colorectal cancer cell line was identified to have the KRAS G12R mutation. No G12R was detected in the parental line despite high-resolution evaluation. Additionally, endogenously expressing KRAS G12R (knock-in) mutation demonstrated resistance to cetuximab treatment, compared to Lim1215 parental cells expressing wild-type KRAS. Resistance was determined by assessing cell viability. |
| KRAS G12R |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced response to panitumumab compared to wildtype KRAS (HR:0.99, 95% CI:0.73-1.36 vs. HR:0.45, 95% CI:0.34-0.59; P<0.0001). Additionally, patients with KRAS mutations showed no significant improvement between treatment with panitumumab and best supportive care alone (PFS: 7.4 wk vs 7.3 wk). |
| KRAS G12S |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced response to panitumumab compared to wildtype KRAS (HR:0.99, 95% CI:0.73-1.36 vs. HR:0.45, 95% CI:0.34-0.59; P<0.0001). Additionally, patients with KRAS mutations showed no significant improvement between treatment with panitumumab and best supportive care alone (PFS: 7.4 wk vs 7.3 wk). |
| KRAS G12V |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, human colorectal cancer cells harboring KRAS G12V were resistant to Erbitux (cetuximab) in culture. |
| KRAS G12V |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
Cells harboring KRAS G12V mutation were insensitive to cetuximab treatment in isogenic SW48 cells and in a mouse xenograft model. |
| KRAS G12V |
KRAS |
Cetuximab, Regorafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring KRAS G12V in culture. |
| KRAS G12V |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced response to panitumumab compared to wildtype KRAS (HR:0.99, 95% CI:0.73-1.36 vs. HR:0.45, 95% CI:0.34-0.59; P<0.0001). Additionally, patients with KRAS mutations showed no significant improvement between treatment with panitumumab and best supportive care alone (PFS: 7.4 wk vs 7.3 wk). |
| KRAS G12X |
KRAS |
5-fluorouracil, Irinotecan, Oxaliplatin, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in patients with KRAS exon 2 mutant colorectal cancer. |
| KRAS G12X |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Vectibix (panitumumab) did not demonstrate efficacy in patients with metastatic colorectal cancer harboring KRAS mutations in codons 12 or 13. |
| KRAS G12X, KRAS G13X, PIK3CA MUTATION |
KRAS PIK3CA |
Bevacizumab, Temsirolimus | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colorectal cancer patient harboring a PIK3CA mutation and KRAS mutations at codons 12 and 13 demonstrated stable disease when treated with a combination of Torisel (temsirolimus) and Avastin (bevacizumab). |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Response to Cetuximab With or Without Irinotecan in Patients With Refractory Metastatic Colorectal Cancer Harboring the KRAS G13D Mutation: Australasian Gastro-Intestinal Trials Group ICECREAM Study. |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Meta-analysis encompassing eight randomized controlled trials (n = 5967) for assessment of both overall survival (OS) and progression-free survival (PFS) of patients with KRAS mutant metastatic colorectal cancer. For other KRAS MT the hazard ratio for OS benefit with addition of anti-EGFR mAb therapy was 1.06 (95% confidence interval [CI]; 0.96, 1.17), compared to 1.08 (95% CI; 0.73, 1.60) for KRAS G13D [test for interaction p=0.99]. In contrast, the hazard ratio for KRAS wild-type (WT) tumours was 0.85 (95% CI; 0.76, 0.95). Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was 1.07 (95% CI; 0.92, 1.26) for other KRAS MT, 0.96 (95% CI; 0.73, 1.27) for KRAS G13D, and 0.68 (95% CI; 0.54, 0.85) for KRAS wild-type. Again, the test for interaction (p=0.46) demonstrated no significant difference in PFS benefit for anti-EGFR mAb therapy between KRAS G13D and other KRAS MT. |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, KRAS mutations in codon 12 or 13 were associated with resistance to Erbitux (cetuximab) in colorectal cancer patients. |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
In an in vitro study, a Lim1215 colorectal cancer cell line endogenously expressing KRAS G13D mutation demonstrated resistance to cetuximab treatment, compared to Lim1215 parental cells expressing wild-type KRAS. Resistance was determined by assessing cell viability. |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 148 treatment naive metastatic colorectal cancer patients, patients with RAS mutations (n=10), including KRAS A146T, KRAS G13D, NRAS G12D and NRAS Q179*, treated with FOLFOX4 plus cetuximab were associated with decreased overall survival (16.3mo vs. 28.5mo, HR:0.43, 95% CI:0.20-0.89, P=0.020) and decreased progression free survival (7.2mo vs. 9.7mo, HR:0.56, 95% CI:0.27-1.16, P=0.11), as compared to patients with wild-type KRAS and NRAS. |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
This is a retrospective analysis of 98 patients with metastatic colorectal cancer and KRAS mutations. 23 (23.5%) had KRAS p.G13D-mutated tumors. Of the 98 patients, 31 patients received cetuximab, of these, 9 (29.0%) had KRAS p.G13D mutations. Univariate analysis did not show any differences between these groups. Multivariate analysis showed a trend towards better PFS among patients with a G13D mutation (PFS: HR=0.29; 95% CI: 0.08-1.10; P=0.07; OS: HR=0.23; 95% CI: 0.04-1.54; P=0.13). |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In cell line model G13D KRAS MASI conferred resistance to cetuximab treatment. CONCLUSIONS: KRAS MASI is a significant event in colorectal cancer, specifically associated with G13D mutation, and featuring a heterogeneous spatial distribution, that may have a role to predict the response to EGFR inhibitors. |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
12 patients with KRAS G13D mutant, metastatic colorectal cancer were treated with single agent cetuximab in a prospective phase II study. The primary endpoint of the trial was 4-month progression-free survival, with a benefit to treatment evaluated to be 50% of patients were progression free at this point. None of 12 patients achieved response by RECIST 1.1 criteria and three patients (25%) were progression-free at 4 months, with disease control rate at 6 months reaching 0%. Median PFS and OS were 1.9 (95% CI 1.7-3.8) and 7.2 months (95% CI 5.7-9.7). |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
KRAS G13D mutation is associated with better response to Cetuximab with longer progression-free and overall survival in colorectal patients compared to other KRAS. |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In vitro and mouse model analysis showed that although p.G12V-mutated colorectal cells were insensitive to cetuximab, p.G13D-mutated cells were sensitive, as were KRAS wild-type cells. |
| KRAS G13D |
KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Cells harboring KRAS G13D mutation were sensitive to cetuximab treatment in isogenic SW48 cells and in a mouse xenograft model. |
| KRAS G13D |
KRAS |
Cetuximab, Irinotecan | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
An assessment of the efficacy and safety of cetuximab-based treatment was performed in an observation-enriched randomized controlled study comparing the cetuximab alone group (Cet group) and the combination of cetuximab and irinotecan group (CetI group) for KRAS G13D-mutated mCRC in Japan. Cetuximab-based treatment seemed to benefit patients with chemotherapy-resistant, refractory KRAS G13D-mutated mCRC. Our results might support the administration of cetuximab-based treatment for KRAS-mutant mCRC and would be able to provide treatment flexibility in this setting. |
| KRAS G13D |
KRAS |
Cetuximab, Panitumumab | Colorectal Adenocarcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
KRAS p.G13D mutations are associated with sensitivity to anti-EGFR antibody treatment in colorectal cancer cell lines. |
| KRAS G13D |
KRAS |
Cetuximab, Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
KRAS G13D Mutation and Sensitivity to Cetuximab or Panitumumab in a Colorectal Cancer Cell Line Model. RESULTS: After treatment with cetuximab or panitumumab, at the optimum concentration of 8 g/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line SW480 and the sensitive KRAS wild-type cell line LIM1215. One of the G13D cell lines was significantly more sensitive to panitumumab than to cetuximab (P = .02). |
| KRAS G13D |
KRAS |
Cetuximab, Regorafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis in human colorectal cancer cell lines harboring KRAS G13D in culture. |
| KRAS G13D |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced response to panitumumab compared to wildtype KRAS (HR:0.99, 95% CI:0.73-1.36 vs. HR:0.45, 95% CI:0.34-0.59; P<0.0001). Additionally, patients with KRAS mutations showed no significant improvement between treatment with panitumumab and best supportive care alone (PFS: 7.4 wk vs 7.3 wk). |
| KRAS G13D, PIK3CA D549N, PIK3CA E545K |
KRAS PIK3CA |
Cetuximab, Regorafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring KRAS G13D, PIK3CA E545K, and PIK3CA D549N in culture and reduced tumor growth in cell line xenograft models. |
| KRAS G13D, PIK3CA H1047R |
KRAS PIK3CA |
Cetuximab, Regorafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring KRAS G13D and PIK3CA H1047R in culture, and reduced tumor growth in cell line xenograft models. |
| KRAS G13X |
KRAS |
5-fluorouracil, Irinotecan, Oxaliplatin, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in patients with KRAS exon 2 mutant colorectal cancer. |
| KRAS G13X |
KRAS |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Vectibix (panitumumab) did not demonstrate efficacy in patients with metastatic colorectal cancer harboring KRAS mutations in codons 12 or 13. |
| KRAS MUTATION |
KRAS |
5-fluorouracil, Irinotecan, Oxaliplatin, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with KRAS mutations. |
| KRAS MUTATION |
KRAS |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a systematic review of 2,266 colorectal cancer patients, treatment with Avastin (bevacizumab) increased progression-free survival in patients harboring wild-type KRAS but not in patients with mutant KRAS. |
| KRAS MUTATION |
KRAS |
Bevacizumab, Oxaliplatin | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Meta-Analysis of 12 studies with 2,266 patients (54 % were KRAS wt). The pooled response rates (RR) for KRAS wild-type (wt) versus mutated (mut) patients were 54.8 and 48.3 %, respectively (OR 1.42, P = 0.02). Median PFS in KRAS wild-type patients was significantly longer than in KRAS mut patients (HR = 0.85; 95 % confidence interval (CI) 0.74-0.98; P = 0.02). Median OS in wild-type KRAS patients compared was significantly better than in KRAS mut patients (HR = 0.65; 95 % CI 0.46-0.92; P = 0.01). |
| KRAS MUTATION |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed a response to cetuximab whereas 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. |
| KRAS MUTATION |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical case report, an acquired KRAS mutation was associated with resistance to Erbitux (cetuximab) in a patient with metastatic colorectal cancer. |
| KRAS MUTATION |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, KRAS mutations were associated with resistance to Erbitux (cetuximab) in patients with colorectal cancer. |
| KRAS MUTATION |
KRAS |
Cetuximab, Dasatinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Combined treatment with dasatinib and cetuximab, but not either agent in monotherapy, had an antitumor efficacy in-vitro and in xenografts. These results were based on three KRAS mutant cell lines (LS180, LoVo and HCT116) and two KRAS wild-type cell lines (SW48 and CaCo2). |
| KRAS MUTATION |
KRAS |
Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis of a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI did not demonstrate an improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with RAS mutations. |
| KRAS MUTATION |
KRAS |
Cetuximab, LSN3074753 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring KRAS mutations, resulted in a disease control rate of 41.7% (5/12). |
| KRAS MUTATION |
KRAS |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Guidelines |
Publications Database: CIViC |
NCCN guidelines indicate colorectal cancer patients with KRAS mutations should not be treated with the anti-EGFR therapies cetuximab or panitumumab. |
| KRAS MUTATION |
KRAS |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
A phase I study to determine the tolerability and pharmacokinetics of Selumetinib and Cetuximab with an expanded cohort in KRAS-mutant CRC. In the KRAS-mutant CRC dose expansion cohort 14 patients were evaluable for response. Five patients experienced stable disease, nine had progressive disease. Minimal anti-tumor activity was observed in KRAS-mutant refractory metastatic CRC. |
| KRAS MUTATION |
KRAS |
FOLFIRI Regimen, Ramucirumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Cyramza (ramucirumab) followed by FOLFIRI was equally efficacious in metastatic colorectal carcinoma patients with Kras exon 2 mutations as patients with wild-type Kras. |
| KRAS MUTATION, PIK3CA E545K |
KRAS PIK3CA |
Buparlisib (BKM-120), Cetuximab | Malignant Colon Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Buparlisib (BKM120) worked synergistically with Erbitux (cetuximab) to inhibit proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA E545K in culture. |
| KRAS MUTATION, PIK3CA E545K |
KRAS PIK3CA |
Cetuximab | Malignant Colon Neoplasm | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) did not inhibit proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA E545K in culture. |
| KRAS MUTATION, PIK3CA H1047R |
KRAS PIK3CA |
Buparlisib (BKM-120), Cetuximab | Malignant Colon Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Buparlisib (BKM120) worked synergistically with Erbitux (cetuximab) to inhibit proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA H1047R in culture. |
| KRAS MUTATION, PIK3CA H1047R |
KRAS PIK3CA |
Cetuximab | Malignant Colon Neoplasm | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) did not inhibit proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA H1047R in culture. |
| KRAS MUTATION, PIK3CA WILD TYPE |
KRAS PIK3CA |
Buparlisib (BKM-120), Cetuximab | Malignant Colon Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Buparlisib (BKM120) worked synergistically with Erbitux (cetuximab) to inhibit proliferation of colon cancer cell lines harboring mutant KRAS and wild-type PIK3CA in culture and tumor growth in xenograft models. |
| KRAS ONCOGENIC MUTATION |
KRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
Publications Database: CGI |
- |
| KRAS ONCOGENIC MUTATION |
KRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
Publications Database: CGI |
- |
| KRAS Q22* |
KRAS |
Panitumumab | Colon Mucinous Adenocarcinoma | Resistant | Clinical |
Publications Database: CIViC |
A 43-year-old female was diagnosed with an adenocarcinoma of the ascending colon and received 6-months of adjuvant chemotherapy. After 5 years of completion of adjuvant chemotherapy, the disease relapsed. EGFR was assessed by immunohistochemistry, and the patient was subsequently treated with the anti-EGFR monoclonal antibody panitumumab. However, there was a rapid clinical worsening, which may possibly be attributed to a somatic mutation in KRAS (Q22*). |
| KRAS Q61H |
KRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a colorectal cancer patient with a KRAS Q61H mutation, KRAS Q61H was reported to be refractory to cetuximab treatment. The patient was treated with cetuximab and irinotecan for 18 months, had a partial response to therapy and then experienced progressive disease with a re-biopsy of the tumor identifying a KRAS Q61H mutation. |
| KRAS WILD TYPE |
KRAS |
5-fluorouracil, Irinotecan, Oxaliplatin, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with KRAS exon 2 wild-type colorectal cancer compared to FOLFIRI treatment alone, with an overall response rate of 35% (105/297) with the combination versus 10% (28/285) with FOLFIRI alone. |
| KRAS WILD TYPE |
KRAS |
5-fluorouracil, Irinotecan, Oxaliplatin, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with RAS wild-type colorectal cancer compared to FOLFIRI treatment alone. |
| KRAS WILD TYPE |
KRAS |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a systematic review of 2,266 colorectal cancer patients, treatment with Avastin (bevacizumab) resulted in improved objective response rate (54.8% vs 48.3%, OR=1.42, p=0.02), median progression-free survival (HR=0.85, p=0.02), and median overall survival (HR=0.65, p=0.01) in KRAS wild-type patients compared to KRAS mutant patients. |
| KRAS WILD TYPE |
KRAS |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, addition of Erbitux (cetuximab) or Avastin (bevacizumab) to chemotherapy (FOLFIRI or mFOLFOX6) resulted in similar median overall survival (30.0 vs 29.0 months, HR=0.88, p=0.08) and median progression-free survival (10.5 vs 10.6 months, HR=0.95, p?=?0.45) in KRAS wild-type colorectal cancer patients. |
| KRAS WILD TYPE |
KRAS |
Bevacizumab, Capecitabine | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Avastin (bevacizumab) and Xeloda (capecitabine) maintenance treatment resulted in better time to first progression (HR = 0.27), time to second progression (HR = 0.42) and overall survival (HR = 0.64) in KRAS wild-type colorectal cancer patients compared to patients harboring KRAS mutations (HR = 0.40, 0.75, 1.07 respectively) (J Clin Oncol 34, 2016 (suppl; abstr 3525)). |
| KRAS WILD TYPE |
KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, addition of Erbitux (cetuximab) or Avastin (bevacizumab) to chemotherapy (FOLFIRI or mFOLFOX6) resulted in similar median overall survival (30.0 vs 29.0 months, HR=0.88, p=0.08) and median progression-free survival (10.5 vs 10.6 months, HR=0.95, p=0.45) in KRAS wild-type colorectal cancer patients. |
| KRAS WILD TYPE |
KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, KRAS wild-type colorectal cancer patients demonstrated a greater response to Erbitux (cetuximab) treatment compared to KRAS mutant colorectal cancer patients, including an objective response of 41% (27/66) vs 0% (0/42), a median overall survival of 43 weeks vs 27.3 weeks, and an overall survival of 74.9 weeks vs 30.6 weeks, respectively. |
| KRAS WILD TYPE |
KRAS |
Cetuximab, Dasatinib, FOLFOX | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, the combination of Erbitux (cetuximab), Sprycel (dasatinib), and FOLFOX demonstrated minimal clinical benefit in patients with metastatic colorectal adenocarcinoma, with an overall response rate of 20% (6/30) in the Phase Ib portion, and 13% (3/24) in KRAS codon 12/13 wild-type patients in the Phase II portion. |
| KRAS WILD TYPE |
KRAS |
Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI demonstrated a significant clinical benefit in OS, PFS, and objective response compared to FOLFIRI alone in colorectal cancer patients with RAS wild-type status. |
| KRAS WILD TYPE |
KRAS |
Cetuximab, Lenalidomide | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, Erbitux (cetuximab) and Revlimid (lenalidomide) combination therapy resulted in partial response in 5% (1/19) and stable disease in 32% (6/19) of KRAS wild-type colorectal cancer patients, and induced Revlimid (lenalidomide) dose-dependent increase of antibody-dependent cellular cytotoxicity. |
| KRAS WILD TYPE |
KRAS |
Napabucasin (BBI-608), Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II clinical trial, BBI608 and Vectibix (panitumumab) combination therapy resulted in PR in 22.2% (2/9), SD in 22.2% (2/9), and median PFS of 9 weeks in colorectal cancer patients carrying wild-type Kras naive for anti-EGFR therapy; compared to SD in 53.3% (8/15), and median PFS of 16.4 weeks in patients failed anti-EGFR treatment (J Clin Oncol 33, 2015 (suppl; abstr 3617)). |
| KRAS WILD TYPE |
KRAS |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a post-hoc analysis of a Phase III trial, colorectal cancer patients with KRAS wild-type demonstrated a greater overall survival (8.1 mo) upon treatment with Vectibix (panitumumab) compared to overall survival (4.4 mo) of patients with KRAS mutations randomized to best supportive care only. |
| KRAS WILD TYPE |
KRAS |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Vectibix (panitumumab) treatment resulted in better overall survival (HR = 0.65) compared to Erbitux (cetuximab) in colorectal cancer patients harboring KRAS with wild-type exon 2 who received prior Avastin (bevacizumab) treatment (J Clin Oncol 34, 2016 (suppl; abstr 3538); NCT01001377). |
| KRAS WILD TYPE |
KRAS |
Panitumumab | Colorectal Carcinoma | Sensitive | Guidelines |
Publications Database: JAX-CKB |
In a Phase III trial that supported FDA approval, Vectibix (panitumumab) demonstrated clinical efficacy only in colorectal cancer patients with wild-type KRAS, resulting in a median progression-free survival of 12.3 weeks, compared to 7.3 weeks with best supportive care (BSC), improved overall survival (HR=0.67), and a response rate of 17% (21/141). |
| KRAS WILD TYPE |
KRAS |
Panitumumab, Cabozantinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib trial, Cometriq (cabozantinib) and Vectibix (panitumumab) combination treatment resulted in a median progression free survival of 3.7 months, median overall survival of 7.5 months, and partial response in 14% (2/14) of KRAS wild-type colorectal patients (J Clin Oncol 34, 2016 (suppl; abstr 3548)). |
| KRAS WILD TYPE |
KRAS |
Panitumumab, Rilotumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, the combination of HGF inhibitor, rilotumumab, with Vectibix (panitumumab) demonstrated efficacy in previously treated patients with wild-type KRAS metastatic colorectal cancer. |
| KRAS WILD TYPE, RS2946834 |
IGF1 KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
In addition, wt KRAS patients harboring IGF1 rs2946834 A/A genotype had a 50% objective response rate compared with 0% for A/G genotype. |
| LIFR D578N |
LIFR |
Bevacizumab, Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
RESULTS: For cetuximab regimens, patients homozygous for the wild-type alleles (GG) of LIFR rs3729740 exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (GA and AA; P=0.022 and 0.027, respectively). Overall response rate gain was achieved up to 10% in patients with wild-type LIFR rs3729740 patients either with wild-type KRAS or skin toxicity (P=0.001) respectively. CONCLUSION: LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed. |
| LIFR D578N |
LIFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
For cetuximab regimens, patients carrying the GG genotype at DFNB31 rs2274159 or LIFR rs3729740 seemed greater chemosensitive than those carrying at least one A allele (P = 0.025 and P = 0.07). |
| LIFR D578N RS361863 |
ISX LIFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Cytotoxicity analyses showed that all RKO and HCT116 CRC clones transfected with the G allele at LIFR rs3729740 and the C allele at ISX rs361863 were more sensitive to cetuximab regimens than those with the A and T allele, respectively (P <= 0.001-0.024). |
| LINS1 I29V |
LINS1 |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Overall responses for bevacizumab regimens revealed that patients carrying the TT genotype at ANXA11 rs1049550 or at least one G allele at LINS1 rs11247226 seemed greater chemosensitive than those carrying at least one C allele or the AA genotype, respectively (P < 0.05). |
| MAP2K1 C121S |
MAP2K1 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, expression of MAP2K1 C121S conferred resistance to Erbitux (cetuximab) in colorectal cancer cells in culture. |
| MAP2K1 C121S |
MAP2K1 |
Cetuximab, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring MAP2K1 C121S in culture. |
| MAP2K1 F53L |
MAP2K1 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, expression of MAP2K1 F53L conferred resistance to Erbitux (cetuximab) in colorectal cancer cells in culture. |
| MAP2K1 F53L |
MAP2K1 |
Cetuximab, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring MAP2K1 F53L in culture. |
| MAP2K1 K57N |
MAP2K1 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines expressing MAP2K1 K57N were insensitive to Erbitux (cetuximab) in culture. |
| MAP2K1 K57N |
MAP2K1 |
Cetuximab, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57N in culture. |
| MAP2K1 K57N |
MAP2K1 |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines expressing MAP2K1 K57N were insensitive to Vectibix (panitumumab) in culture. |
| MAP2K1 K57N |
MAP2K1 |
Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Vectibix (panitumumab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57N in culture. |
| MAP2K1 K57T |
MAP2K1 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, a patient with colorectal cancer developed liver metastases harboring MAP2K1 K57T that were insensitive to Erbitux (cetuximab) treatment and the mutation was confirmed to cause resistance in human colorectal cancer cell lines in culture. |
| MAP2K1 K57T |
MAP2K1 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Biopsy of a patients progressing liver metastasis following prolonged response to cetuximab revealed a MEK1(K57T) mutation as a novel mechanism of acquired resistance. |
| MAP2K1 K57T |
MAP2K1 |
Cetuximab, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57T in culture. |
| MAP2K1 K57T |
MAP2K1 |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a colorectal cancer cell line expressing MAP2K1 K57T was resistant to Vectibix (panitumumab) in culture. |
| MAP2K1 K57T |
MAP2K1 |
Panitumumab, Trametenib | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Biopsy of a patients progressing liver metastasis following prolonged response to cetuximab revealed a MEK1(K57T) mutation as a novel mechanism of acquired resistance. This lesion regressed upon treatment with panitumumab and the MEK inhibitor trametinib. |
| MAP2K1 K57T |
MAP2K1 |
Panitumumab, Trametinib | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer. |
| MAP2K1 K57T |
MAP2K1 |
Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, a combination of Vectibix (panitumumab) and Mekinist (trametinib) caused tumor regression in a patient's colorectal cancer metastases harboring MAP2K1 K57T after being identified pre-clinically as a combination likely to inhibit MAP2K1 K57T expressing colorectal cancer. |
| MED1 MUTATION |
MED1 |
Tamoxifen, Trastuzumab | Breast Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
These included an activating mutation in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) following treatment with paclitaxel; a truncating mutation in RB1 (retinoblastoma 1) following treatment with cisplatin; a truncating mutation in MED1 (mediator complex subunit 1) following treatment with tamoxifen and trastuzumab, and following subsequent treatment with lapatinib, a splicing mutation in GAS6 (growth arrest-specific 6) in the same patient; and a resistance-conferring mutation in EGFR (epidermal growth factor receptor; T790M) following treatment with gefitinib. These results establish proof of principle that exome-wide analysis of circulating tumour DNA could complement current invasive biopsy approaches to identify mutations associated with acquired drug resistance in advanced cancers. |
| MET AMPLIFICATION |
MET |
Cabozantinib, Panitumumab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
- |
| MET AMPLIFICATION |
MET |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, MET amplification was associated with resistance to Erbitux (cetuximab) in 2 colorectal cancer patients, and in patient-derived xenograft (PDX) models. |
| MET AMPLIFICATION |
MET |
Cetuximab, Crizotinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Functional studies show that MET activation confers resistance to anti-EGFR therapy both in vitro and in vivo. Notably, in patient-derived colorectal cancer xenografts, MET amplification correlated with resistance to EGFR blockade, which could be overcome by MET kinase inhibitors. |
| MET OVEREXPRESSION |
MET |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, over expression of MET conferred resistance to Erbitux (cetuximab) in colorectal cancer cell lines in culture. |
| MET OVEREXPRESSION |
MET |
Cetuximab, JNJ-38877605 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the addition of JNJ-38877605 to Erbitux (cetuximab) treatment overcame Erbitux (cetuximab) resistance in colorectal cancer cell lines over expressing MET in culture. |
| MET OVEREXPRESSION |
MET |
JNJ-38877605, Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the addition of JNJ-38877605 to Vectibix (panitumumab) treatment overcame Vectibix (panitumumab) resistance in colorectal cancer cell lines over expressing MET in culture. |
| MET OVEREXPRESSION |
MET |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, over expression of MET conferred resistance to Vectibix (panitumumab) in colorectal cancer cell lines in culture. |
| MIR-125A OVEREXPRESSION |
MIR125A |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-126 OVEREXPRESSION |
MIR126 |
Bevacizumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
CONCLUSIONS: The present results indicate that changes in cir-miRNA-126 during treatment are related to the response to chemotherapy and bevacizumab in patients with mCRC, thus representing a possible biomarker for the resistance to anti-angiogenic containing treatments. |
| MIR-126 OVEREXPRESSION |
MIR126 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-129 OVEREXPRESSION |
MIR129 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Trastuzumab is an important treatment used for patients with Her-2-positive breast cancer, but an increasing incidence of trastuzumab resistance has been observed clinically during the past decade. Aberrant microRNA (miR) expression levels are correlated with prognosis and response to trastuzumab in breast cancer. MiR-129-5p is downregulated in trastuzumab-resistant human breast cancer cells (JIMT-1), but its potential function and underlying mechanism remain unclear. The effects of miR-129-5p on cell responses to trastuzumab were analyzed by CCK-8 and flow cytometry assays in Her-2-positive breast cancer cells (SKBR-3 and JIMT-1). RESULTS: MiR-129-5p, which was downregulated and predicted to target rpS6 in trastuzumab-resistant breast cancer cells, enhanced the sensitivity of breast cancer cells to trastuzumab by reducing the expression of rpS6. |
| MIR-152 OVEREXPRESSION |
MIR152 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-17 OVEREXPRESSION |
MIR17 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-17 OVEREXPRESSION |
MIR17 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
On the basis of these data, we suggest that the downregulation of let-7b and let-7e (targeting K-ras) and the upregulation of miR-17* (a CRC marker) could be considered as candidate molecular markers of cetuximab resistance. |
| MIR-182 OVEREXPRESSION |
MIR182 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-182 OVEREXPRESSION |
MIR182 |
Trastuzumab | Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
Cell viability, apoptosis, colony formation, and migration capacities of SKBR3(S) (sensitive) and SKBR3(R) (resistant) cells were assessed to determine the anti-proliferative effects of PNA-antimiR-182. In line with that, PNA-antimiR-182 inhibited synergistically the viability of both the sensitive and resistant cell groups. In line with that, PNA-antimiR-182 inhibited synergistically the viability of both the sensitive and resistant cell groups. Consequently, downregulation of miR-182 might find therapeutical value for overcoming trastuzumab resistance. |
| MIR-18A OVEREXPRESSION |
MIR18A |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-190B UNDEREXPRESSION |
MIR190B |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-199A OVEREXPRESSION |
MIR199A1 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
We report that their enforced expression promotes CTX resistance, whereas their silencing sensitizes to the same drug. |
| MIR-199B OVEREXPRESSION |
MIR199B |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-19B OVEREXPRESSION |
MIR19B1 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-200C RESTORATION |
MIR200C |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Restoration of miR-200c, silencing of ZEB1 or ZNF217 or blockade of TGF-b signaling increased trastuzumab sensitivity and suppressed invasiveness of breast cancer cells. |
| MIR-200C RESTORATION |
MIR200C |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Restoration of miR-200c, silencing of ZEB1 or ZNF217 or blockade of TGF-b signaling increased trastuzumab sensitivity and suppressed invasiveness of breast cancer cells. |
| MIR-203 OVEREXPRESSION |
MIR203A |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-21 OVEREXPRESSION |
MIR21 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-21 OVEREXPRESSION |
MIR21 |
Trastuzumab | Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
Blocking the action of miR-21 with antisense oligonucleotides re-sensitized the resistant cells to the therapeutic activities of trastuzumab by inducing growth arrest, proliferation inhibition, and G(1)-S cell cycle checking in the presence of the antibody. |
| MIR-21 OVEREXPRESSION |
MIR21 |
Trastuzumab | Breast Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. Here, we demonstrated that miR-21 expression was up-regulated and its function was elevated in HER2(+) BT474, SKBR3, and MDA-MB-453 breast cancer cells that are induced to acquire trastuzumab resistance by long-term exposure to the antibody, whereas protein expression of the PTEN gene, a miR-21 target, was reduced. Here, we demonstrated that miR-21 expression was up-regulated and its function was elevated in HER2(+) BT474, SKBR3, and MDA-MB-453 breast cancer cells that are induced to acquire trastuzumab resistance by long-term exposure to the antibody, whereas protein expression of the PTEN gene, a miR-21 target, was reduced. Therefore, miR-21 overexpression contributes to trastuzumab resistance in HER2(+) breast cancers and antagonizing miR-21 demonstrates therapeutic potential by sensitizing the malignancy to anti-HER2 treatment. Therefore, miR-21 overexpression contributes to trastuzumab resistance in HER2(+) breast cancers and antagonizing miR-21 demonstrates therapeutic potential by sensitizing the malignancy to anti-HER2 treatment. |
| MIR-21 OVEREXPRESSION |
MIR21 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN (rs = -0.502; p = 0.005) and PDCD4 (rs = -0.426; p = 0.019), which differentially influenced the drug sensitivity of HER2-positive breast cancer cells. We further demonstrated that miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-kB-mediated signaling loop and activating the PI3K pathway. Collectively, these data provide a rationale for using miR-21 expression as a biomarker to select trastuzumab-chemotherapy-resistant HER2-positive breast cancer patients who may benefit from treatments containing PI3K inhibitors or immunomodulatory drugs. |
| MIR-21 OVEREXPRESSION |
MIR21 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN (rs = -0.502; p = 0.005) and PDCD4 (rs = -0.426; p = 0.019), which differentially influenced the drug sensitivity of HER2-positive breast cancer cells. We further demonstrated that miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-kB-mediated signaling loop and activating the PI3K pathway. Collectively, these data provide a rationale for using miR-21 expression as a biomarker to select trastuzumab-chemotherapy-resistant HER2-positive breast cancer patients who may benefit from treatments containing PI3K inhibitors or immunomodulatory drugs. |
| MIR-210 OVEREXPRESSION |
MIR210 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Our results suggest that high relative expression levels for miRNA-210 in the plasma of breast cancer patients are associated with trastuzumab resistance and the presence of the tumor. |
| MIR-210 OVEREXPRESSION |
MIR210 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
At baseline before Patient received neoadjuvant chemotherapy combined with trastuzumab, circulating miR-210 levels were significantly higher in those who had residual disease than in those who achieved a pathologic complete response (P = .0359). |
| MIR-219-2 OVEREXPRESSION |
MIR219A2 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-221 OVEREXPRESSION |
MIR221 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-221 OVEREXPRESSION |
MIR221 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
Here, we found that the oncogenic miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted metastasis of HER2-positive breast cancers. |
| MIR-221 OVEREXPRESSION |
MIR221 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN. Here, we found that the oncogenic miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted metastasis of HER2-positive breast cancers. These findings indicate that miR-221 may promote trastuzumab resistance and metastasis of HER2-positive breast cancers by targeting PTEN, suggesting its role as a potential biomarker for progression and poor prognosis, and as a novel target for trastuzumab-combined treatment of breast cancers. |
| MIR-26A OVEREXPRESSION |
MIR26A1 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-27B OVEREXPRESSION |
MIR27B |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-296 OVEREXPRESSION |
MIR296 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-29C OVEREXPRESSION |
MIR29C |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-337 OVEREXPRESSION |
MIR337 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-339 OVEREXPRESSION |
MIR339 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-375 OVEREXPRESSION |
MIR375 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
We report that their enforced expression promotes CTX resistance, whereas their silencing sensitizes to the same drug. |
| MIR-375 OVEREXPRESSION |
MIR375 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Overexpression of miR-375 restored the sensitivity of cells to trastuzumab, while inhibition of miR-375 conferred trastuzumab resistance on HER2-positive breast cancer cells. CONCLUSIONS: Epigenetic silencing of miR-375 causes the upregulation of IGF1R, which at least partially underlies trastuzumab resistance of breast cancer cells. |
| MIR-377 UNDEREXPRESSION |
MIR377 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-378A OVEREXPRESSION |
MIR378A |
Cetuximab,, Lauric, Acid | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
After the increase of miR-378 in cells by either direct or indirect approaches, sensitivity to Cetuximab was restored in all BRAF mutants (p-value <0.0001-0.0003), and half of KRAS mutants CRC (p-value 0.039-0.007). In conclusion, the present study demonstrated that lauric acid may efficiently induce miR-378 expression in CRC mutants, and both BRAF and a subtype of KRAS mutants presented significantly improved sensitivity to Cetuximab. |
| MIR-383 UNDEREXPRESSION |
MIR383 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-451 OVEREXPRESSION |
MIR451A |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-498 UNDEREXPRESSION |
MIR498 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-516B UNDEREXPRESSION |
MIR516B1 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-542 UNDEREXPRESSION |
MIR542 |
Trastuzumab | Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
Furthermore, knockdown of miRNA-542-3p in the two cell lines resulted in decreased drug sensitivity to trastuzumab and cell apoptosis. |
| MIR-595 UNDEREXPRESSION |
MIR595 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-609 UNDEREXPRESSION |
MIR609 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-619 UNDEREXPRESSION |
MIR619 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-640 OVEREXPRESSION |
MIR640 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-654 UNDEREXPRESSION |
MIR654 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-7-1 OVEREXPRESSION |
MIR7-1 |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
miR-7 regulates cetuximab sensitivity in cetuximab-resistant HCT116 and SW480 cells with a KRAS mutation and HT29 cells with a BRAF mutation. |
| MIR-7-1 OVEREXPRESSION |
MIR7-1 |
Trastuzumab | Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Our results demonstrate that reestablished miR-7 expression abolishes HER2delta16 induced cell proliferation and migration while sensitizing HER2delta16 expressing cells to trastuzumab therapy. |
| MIR-768 OVEREXPRESSION |
MIR768 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-769 UNDEREXPRESSION |
MIR769 |
Cetuximab | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIR-801 OVEREXPRESSION | Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. | |
| MIR-99B OVEREXPRESSION |
MIR99B |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIRLET-7B UNDEREXPRESSION |
MIRLET7B |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
On the basis of these data, we suggest that the downregulation of let-7b and let-7e (targeting K-ras) and the upregulation of miR-17* (a CRC marker) could be considered as candidate molecular markers of cetuximab resistance. |
| MIRLET-7D OVEREXPRESSION |
MIRLET7D |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| MIRLET-7E UNDEREXPRESSION |
MIRLET7E |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
On the basis of these data, we suggest that the downregulation of let-7b and let-7e (targeting K-ras) and the upregulation of miR-17* (a CRC marker) could be considered as candidate molecular markers of cetuximab resistance. |
| MIRLET-7F-1 OVEREXPRESSION |
MIRLET7F1 |
Cetuximab | Colon Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
In summary, we found a list of 27 upregulated and 10 downregulated miRNAs with a fold change > 2 in GEO CR with respect to the GEO cells. |
| NF1 MUTATION |
NF1 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, Chinese metastatic colorectal cancer patients harboring either a SMAD4 mutation or NF1 mutation did not respond to treatment with Erbitux (cetuximab) and showed a shorter progression-free survival compared to patients with wild-type SMAD4 or wild-type NF1. |
| NRAS 117 |
NRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
Publications Database: CGI |
Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, // While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| NRAS 117 |
NRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| NRAS 12 |
NRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
Publications Database: CGI |
Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, // While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| NRAS 12 |
NRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| NRAS 13 |
NRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
Publications Database: CGI |
Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, // While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| NRAS 13 |
NRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| NRAS 146 |
NRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
Publications Database: CGI |
Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, // While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| NRAS 146 |
NRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| NRAS 59 |
NRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
Publications Database: CGI |
Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, // While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| NRAS 59 |
NRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| NRAS 61 |
NRAS |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Guidelines |
Publications Database: CGI |
Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, // While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| NRAS 61 |
NRAS |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| NRAS EXON 2 |
NRAS |
Cetuximab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org). |
| NRAS EXON 2 |
NRAS |
Panitumumab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org). |
| NRAS EXON 3 |
NRAS |
Cetuximab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 3 mutations (NCCN.org). |
| NRAS EXON 3 |
NRAS |
Panitumumab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 3 mutations (NCCN.org). |
| NRAS EXON 4 |
NRAS |
Cetuximab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org). |
| NRAS EXON 4 |
NRAS |
Panitumumab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org). |
| NRAS G12D |
NRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 148 treatment naive metastatic colorectal cancer patients, patients with RAS mutations (n=10), including KRAS A146T, KRAS G13D, NRAS G12D and NRAS Q179*, treated with FOLFOX4 plus cetuximab were associated with decreased overall survival (16.3mo vs. 28.5mo, HR:0.43, 95% CI:0.20-0.89, P=0.020) and decreased progression free survival (7.2mo vs. 9.7mo, HR:0.56, 95% CI:0.27-1.16, P=0.11), as compared to patients with wild-type KRAS and NRAS. |
| NRAS G12V |
NRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring NRAS G12V demonstrated resistance to Erbitux (cetuximab) in culture. |
| NRAS G12V |
NRAS |
Cetuximab, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring NRAS G12V in culture. |
| NRAS MUTATION |
NRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed a response to cetuximab whereas 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. |
| NRAS MUTATION |
NRAS |
Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis of a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI did not demonstrate an improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with RAS mutations. |
| NRAS MUTATION |
NRAS |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Guidelines |
Publications Database: CIViC |
NCCN guidelines indicate colorectal cancer patients with NRAS mutations should not be treated with EGFR inhibitors cetuximab or panitumumab. |
| NRAS Q179X |
NRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 148 treatment naive metastatic colorectal cancer patients, patients with RAS mutations (n=10), including KRAS A146T, KRAS G13D, NRAS G12D and NRAS Q179*, treated with FOLFOX4 plus cetuximab were associated with decreased overall survival (16.3mo vs. 28.5mo, HR:0.43, 95% CI:0.20-0.89, P=0.020) and decreased progression free survival (7.2mo vs. 9.7mo, HR:0.56, 95% CI:0.27-1.16, P=0.11), as compared to patients with wild-type KRAS and NRAS. |
| NRAS Q61 |
NRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In chemotherapy-refractory patients with colorectal cancer, NRAS mutation status (primarily Q61) was not informative for disease control rate, progression free survival or overall survival following cetuximab plus chemotherapy. |
| NRAS Q61 |
NRAS |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Chemotherapy-refractory patients with colorectal cancer harboring NRAS mutation (primarily Q61) have a significantly lower response rate to cetuximab than patients wildtype for NRAS. |
| NRAS WILD TYPE |
NRAS |
Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI demonstrated a significant clinical benefit in OS, PFS, and objective response compared to FOLFIRI alone in colorectal cancer patients with RAS wild-type status. |
| NRAS WILD TYPE |
NRAS |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with RAS wild-type colorectal cancer compared to FOLFIRI treatment alone. |
| NRG1 OVEREXPRESSION |
NRG1 |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
NRG1 upregulation or ERBB2 amplification were the main causes of resistance to cetuximab in-vivo and in-vitro in this study. Inhibition of ERBB2/ERBB3 signaling restored cetuximab sensitivity. |
| NT5E OVEREXPRESSION |
NT5E |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
CD73 high expression was identified as a potential marker of improved PFS from cetuximab treatment in patients with metastatic CRC. |
| PIK3CA E542K |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing PIK3CA E542K were resistant to Erbitux (cetuximab) and Fluorouracil combination treatment in culture. |
| PIK3CA E542K |
PIK3CA |
Cetuximab, Irinotecan | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, treatment with the combination of Erbitux (cetuximab) and Camptosar (irinotecan) resulted in partial response in 50% (1/2) and stable disease in 50% (1/2) of colorectal carcinoma patients harboring a PIK3CA E542K mutation. |
| PIK3CA E542K |
PIK3CA |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
The presence of a PIK3CA mutation in exon 9 (such as E542K) or exon 20 were associated with lack of panitumumab or cetuximab response. |
| PIK3CA E542V |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, Erbitux (cetuximab) treatment resulted in stable disease in a colorectal carcinoma patient harboring a PIK3CA E542V mutation. |
| PIK3CA E545K |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing PIK3CA E545K were resistant to Erbitux (cetuximab) and Fluorouracil combination treatment in culture. |
| PIK3CA E545K |
PIK3CA |
Cetuximab, Irinotecan | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, treatment with the combination of Erbitux (cetuximab) and Camptosar (irinotecan) resulted in stable disease in 50% (1/2) and 14 months without evidence of disease in 50% (1/2) of colorectal carcinoma patients harboring a PIK3CA E545K mutation. |
| PIK3CA E545K |
PIK3CA |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In metastatic colorectal cancer, the objective tumor response rate to the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab or panitumumab was lower in patients with PIK3CA mutations (23% vs. 0%, P=0.038, univariate analysis; odds ratio:0.1153, 95% CI:0.000-0.865, P=0.0337, multivariate analysis) compared to wildtype patients. |
| PIK3CA E545K |
PIK3CA |
Trastuzumab | Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
RESULTS: Four cell lines with PIK3CA mutations (E545K and H1047R) were more resistant to trastuzumab than the remaining four without mutations (mean percentage of control with 10 microg/ml trastuzumab: 58% versus 92%; P = 0.010). PIK3CA mutations are associated with resistance to HER2-targeted agents. |
| PIK3CA E545K |
PIK3CA |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
PI3K mutant E545K was overexpressed in the trastuzumab sensitive HER2 BT474 breast cancer cell line, and significant resistance to trastuzumab was induced in comparison to control cells. |
| PIK3CA E545K |
PIK3CA |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Clinical |
Publications Database: CIViC |
In HER2-positive metastic breast cancer patients treated with trastuzumab-based therapy, the presence of a PIK3CA mutation was associated with an increased risk of progression (HR:2.50, 95% CI:1.35-4.61, P=0.003, univariate analysis; HR:1.86, 95% CI:1.13-3.05, P=0.014, multivariate analysis) and reduced time to progression (HR:2.50, 95% CI:1.35-4.61, P=0.003) compared to wildtype PIK3CA. |
| PIK3CA E545K |
PIK3CA |
Trastuzumab Emtansine | Malignant Breast Neoplasm | Sensitive | Clinical |
Publications Database: CIViC |
In a phase 3 clinical trial (NCT00829166), metastatic breast cancer patients with PIK3CA mutation (n=40), including patients with PIK3CA E545K, treated with ado-trastuzumab were associated with improved median progression free survival (10.9 vs. 9.8 months), as compared to patients with wild-type PIK3CA (n=93). Further, the patients harboring PIK3CA mutations (n=79) were associated with a decrease in disease progression (ado-trastuzumab relative to standard chemotherapy; HR:0.45; 95% CI:0.25-0.82), as compared to patients with wild-type PIK3CA (n=180; HR:0.74; 95% CI:0.50-1.10). In an in vitro study, MCF7 cell lines expressing PIK3CA E545K mutation was associated with increased sensitivity to ado-trastuzumab emtansine treatment compared to trastuzumab treated MCF7 cells. Sensitivity was determined by assessing cell viability. Further, in an in vivo study, MCF7 xenografts expressing PIK3CA E545K were reportedly sensitive to ado-trastuzumab emtansine, as assessed by tumor growth. |
| PIK3CA EXON 21 MUTATION |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Chemotherapy-refractory patients with colorectal cancer harboring Exon 20 PIK3CA mutations had lower response and disease control rates as well as shorter progression free and overall survival following cetuximab plus chemotherapy than those with wildtype PIK3CA. |
| PIK3CA F930S |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N, p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of cetuximab. The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC. |
| PIK3CA F930S |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, PIK3CA F930S was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in colorectal cancer patients, which is consistent with cell culture studies demonstrating moderate resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA F930S. |
| PIK3CA H1047R |
PIK3CA |
AZD-5363, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Tumor xenografts in mice were established with the KPL4 HER2 positive breast cancer cell line with PIK3CA H1047R mutation. KPL4 has suboptimal responses to trastuzumab and lapatinib. Xengraft treatment with trastuzumab and AZD5363 monotherapy induced moderate growth inhibition which was significant for AZD5363, but co-treatment with trastuzumab and AZD5363 induced significant tumor regression and enhanced growth delay upon removal of treatment. |
| PIK3CA H1047R |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, Erbitux (cetuximab) combined with radiation therapy resulted in stable disease for 6 months in a colorectal carcinoma patient harboring a PIK3CA H1047R mutation. |
| PIK3CA H1047R |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells over expressing PIK3CA H1047R were resistant to Erbitux (cetuximab) and Fluorouracil combination treatment in culture. |
| PIK3CA H1047R |
PIK3CA |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
The presence of a PIK3CA mutation in exon 9 or exon 20 (such as H1047R) were associated with lack of panitumumab or cetuximab response. |
| PIK3CA H1047R |
PIK3CA |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In colorectal cancer, PIK3CA mutations were associated with reduced relapse-free survival in stage II/III patients (HR:2.587, 95% CI:1.108-6.039, P=0.0280, univariate analysis; HR:2.478, 95% CI:1.028-5.973, P=0.0433, multivariate analysis) and reduced disease-specific survival in patients of any stage (n=18 vs. n=140, P=0.0357) compared to wildtype PIK3CA. |
| PIK3CA H1047R |
PIK3CA |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Rectal cancer patients with PIK3CA mutations showed a higher risk of local recurrence (HR:3.5; 95% CI:1.3-9.3, P=0.013, univariate analysis; HR:3.4, 95% CI:1.2-9.2, P=0.017, multivariate analysis) compared to wildtype PIK3CA patients. |
| PIK3CA H1047R |
PIK3CA |
Trastuzumab | Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
RESULTS: Four cell lines with PIK3CA mutations (E545K and H1047R) were more resistant to trastuzumab than the remaining four without mutations (mean percentage of control with 10 microg/ml trastuzumab: 58% versus 92%; P = 0.010). PIK3CA mutations are associated with resistance to HER2-targeted agents. |
| PIK3CA H1047R |
PIK3CA |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Clinical |
Publications Database: CIViC |
In HER2-positive metastic breast cancer patients treated with trastuzumab-based therapy, the presence of a PIK3CA mutation was associated with an increased risk of progression (HR:2.50, 95% CI:1.35-4.61, P=0.003, univariate analysis; HR:1.86, 95% CI:1.13-3.05, P=0.014, multivariate analysis) and reduced time to progression (HR:2.50, 95% CI:1.35-4.61, P=0.003) compared to wildtype PIK3CA. |
| PIK3CA H1047R |
PIK3CA |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Clinical |
Publications Database: CIViC |
In Japanese invasive breast cancer patients, PIK3CA mutation was associated with improved relapse-free survival. |
| PIK3CA H1047R |
PIK3CA |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Preclinical |
Publications Database: CIViC |
Breast cancer cell lines with oncogenic PIK3CA mutations had an increased sensitivity to treatment with class I PI3K inhibitor, GDC-0941 (pictilisib), as compared to wildtype PIK3CA cell lines. |
| PIK3CA H1047R |
PIK3CA |
Trastuzumab Emtansine | Malignant Breast Neoplasm | Sensitive | Clinical |
Publications Database: CIViC |
In a phase 3 clinical trial (NCT00829166), metastatic breast cancer patients with PIK3CA mutation (n=40), including patients with PIK3CA H1047R, treated with ado-trastuzumab were associated with improved median progression free survival (10.9 vs. 9.8 months), as compared to patients with wild-type PIK3CA (n=93). Further, the patients harboring PIK3CA mutations (n=79) were associated with a decrease in disease progression (ado-trastuzumab relative to standard chemotherapy; HR:0.45; 95% CI:0.25-0.82), as compared to patients with wild-type PIK3CA (n=180; HR:0.74; 95% CI:0.50-1.10). In an in vitro study, HCC1954 and KPL-4 cell lines expressing PIK3CA H1047R mutation was associated with increased sensitivity to ado-trastuzumab emtansine treatment compared to trastuzumab treated HCC1954 and KPL-4 cells. Sensitivity was determined by assessing cell viability. Further, in an in vivo study, KPL-4 xenografts expressing PIK3CA H1047R were reportedly sensitive to ado-trastuzumab emtansine, as assessed by tumor growth. |
| PIK3CA H1047X |
PIK3CA |
Bevacizumab, Temsirolimus | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colorectal cancer patient harboring a mutation at PIK3CA H1047 demonstrated progressive disease when treated with Torisel (temsirolimus) and Avastin (bevacizumab). |
| PIK3CA K944N |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N, p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of cetuximab. The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC. |
| PIK3CA K944N |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, PIK3CA K944N was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in colorectal cancer patients, which is supported by cell culture studies demonstrating resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA K944N. |
| PIK3CA K966E |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N, p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of cetuximab. The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC. |
| PIK3CA K966E |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, PIK3CA K966E was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in colorectal cancer patients, which is supported by cell culture studies demonstrating resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA K966E. |
| PIK3CA MUTATION |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed a response to cetuximab and only 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. |
| PIK3CA MUTATION |
PIK3CA |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
The HER2 overexpressing breast cancer cell line BT-474 transduced with mutant PIK3CA H1047R demonstrated essentially normal proliferation under trastuzumab, while control cells showed negligible proliferation with trastuzumab. Sequencing of 55 HER2 breast cancer samples revealed 25% PIK3CA mutation rate and Kaplan Meier curves showed decreased time to progression for mutant PIK3CA at borderline statistical significance (p=0.052). This was potentially explained by presence of PTEN loss in wild-type PIK3CA sample and combining PTEN loss with PIK3CA mutation resulted in significant differences in time to progression (p=0.007). |
| PIK3CA ONCOGENIC MUTATION |
PIK3CA |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies.// While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population. |
| PIK3CA R88Q |
PIK3CA |
Cetuximab, Floxuridine, 5-fluorouracil, Irinotecan | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, treatment with the combination of Erbitux (cetuximab), Adrucil (fluorouracil), Camptosar (irinotecan), and Floxuridine resulted in at least 24 months without evidence of disease in a colorectal carcinoma patient harboring a PIK3CA R88Q mutation. |
| PIK3CA V952A |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, PIK3CA V952A was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in colorectal cancer patients, which is consistent with cell culture studies demonstrating moderate resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA V952A. |
| PIK3CA V955G |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N, p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of cetuximab. The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC. |
| PIK3CA V955G |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, PIK3CA V955G was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in colorectal cancer patients, which is supported by cell culture studies demonstrating resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA V955G. |
| PIK3CA V955I |
PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N, p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of cetuximab. The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC. |
| PIK3CA V955I |
PIK3CA |
Cetuximab, 5-fluorouracil | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, PIK3CA V955I was identified as a potential mechanism for acquired Erbitux (cetuximab) resistance in colorectal cancer patients, which is supported by cell culture studies demonstrating resistance to Erbitux (cetuximab) and Fluorouracil combination treatment in colorectal cancer cells over expressing PIK3CA V955I. |
| PIK3CA WILD TYPE |
PIK3CA |
Lapatinib, Paclitaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial, the combination of Taxol (paclitaxel) plus Herceptin (trastuzumab) and Tykerb (lapatinib) resulted in a higher pathologic complete remission rate in ERBB2 (HER2)-receptor positive breast cancer patients with PIK3CA wild-type compared to those harboring a PIK3CA mutation. |
| PPP1R15A R251P |
PPP1R15A |
Bevacizumab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Exome and RNA sequencing was performed in tumor and matched normal tissue of 19 patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab. The variant PPP1R15A (rs557806) showed the most significant association (P = 0.000401) with FOLFIRI-bevacizumab-driven tumor inhibition rate in exome sequencing data and the highest correlation (r = 0.74) with the drug responses in RNA sequencing data. Patients who were homozygous for the reference alleles (GG) of PPP1R15A rs557806 exhibited greater disease control rates and a tendency toward greater overall response rate than those with homozygous or heterozygous substitution alleles (GC and CC; P = 0.027 and 0.073) when treated with bevacizumab-containing regimens. PPP1R15A rs557806 nonsignificantly correlated with DCR in multivariate analysis (P = 0.054). In HCT116 xenograft tumors, tumor growth IR with FRB was 25 % in mock cells, 24 % in clones with reference alleles (G alleles) of PPP1R15A rs557806, and 17 % in clones with substitution alleles (C alleles) of PPP1R15A rs557806 (P = 0.004, day 13). FDG-PET imaging on day 7 showed FDG uptake (mean SUV max) of 0.219 and 0.500 in HCT116 xenografts expressing the reference allele (G) and substitution allele (C) of PPP1R15A rs557806, respectively (P = 0.032). |
| PPP1R1B TRUNCATION |
PPP1R1B |
Erlotinib, Gefitinib, Trastuzumab | Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
The over-expression of t-Darpp might facilitate enhanced EGFR signaling as part of the trastuzumab resistance phenotype. This study suggests that the presence of t-Darpp in HER2+ cancers might predict the enhanced response to dual HER2/EGFR targeting. |
| PTEN BIALLELIC INACTIVATION |
PTEN |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Caris molecular intelligence Database: CGI |
- |
| PTEN BIALLELIC INACTIVATION |
PTEN |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Clinical |
Caris molecular intelligence Database: CGI |
- |
| PTEN DELETION |
PTEN |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In 27 patients with chemotherapy-naive or chemotherapy-refractory metastatic colorectal cancer who were treated with cetuximab and chemotherapy, PTEN loss was associated with non-response. |
| PTEN DELETION |
PTEN |
LY294002, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Knockdown of PTEN in trastuzumab sensitive HER2 breast cancer BT474 cells induced trastuzumab resistance. PTEN null cells treated with PI3K inhibitor LY294002 also did not show substantial inhibition, but co-treatment with trastuzumab and LY294002 induced growth inhibition comparable to trastuzumab alone in normal BT474 cells. BT474 mouse xenograft tumors were injected with PTEN antisense (AS) oligonucleotides and this resulted in trastuzumab resitance. Co-treatment of PTEN AS tumor mice with LY294002 and trastuzumab inhibited tumor growth in comparison to PTEN AS tumors treated with trastuzumab or LY294002 alone. |
| PTEN DELETION |
PTEN |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
While some reports indicate PTEN loss is associated with resistance to trastuzumab, in a subgroup of HER2 breast cancer FFPE samples from patients receiving trastuzumab as later line therapy (second or greater line therapy), with 25 PTEN loss and and 25 normal samples, no association was seen between trastuzumab response and PTEN status (p=1.000) or overall survival and PTEN status (p=0.863). |
| PTEN DELETION |
PTEN |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
A subgroup of HER2-positive breast cancer patients that received first-line trastuzumab treatment were assessed for PTEN loss via IHC of FFPE samples. 46 samples showed PTEN loss while 41 did not, and PTEN loss alone was found to be significantly associated with resistance to trastuzumab (p=0.028) and shorter overall survival (p=0.008). |
| PTEN DELETION |
PTEN |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
A large-scale RNAi genetic sereen in HER2 overexpressing breast cancer cell line BT-474 was performed to discover genes whose loss induced trastuzumab resistance. The most prominently enriched gene in trastuzumab resistant populations was PTEN. Subsequent knockdown of PTEN in BT-474 cells increased cell survival when treated with trastuzumab, and growth curves showed partial restoration of proliferation in PTEN knockdown BT-474 cells treated with trastuzumab. |
| PTEN DELETION |
PTEN |
Trastuzumab | Malignant Breast Neoplasm | Resistant | Clinical |
Publications Database: CIViC |
PTEN loss is associated with loss of sensitivity to the HER2-antibody trastuzumab in breast cancer in smaller trials, a phase III trial (NCCTG N9831) did not show an effect of PTEN on disease-free survival. |
| PTEN OVEREXPRESSION |
PTEN |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Clinical |
Publications Database: CIViC |
Trastuzumab was more effective in cell lines (SKBR3 vs. drug-resistant SKBR3/R) and 17 patient samples that exhibit elevated PTEN expression (by IHC). |
| PTP4A3 OVEREXPRESSION |
PTP4A3 |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In-vitro studies linked PRL-3 (PP4A3) expression to hyperactivation and dependence on EGFR signaling (through downregulation of PTP1B, an inhibitory phosphatase of EGFR). Retrospective analysis of 68 patients showed improved clinical response to the EGFR inhibitor cetuximab in tumors expressing PRL-3. |
| RS3130 |
PROM1 |
Bevacizumab, Capecitabine, Irinotecan | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
OBJECTIVE: The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity. |
| RS444903 |
EGF |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
RESULTS: The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). |
| RS4975596 |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
We show that allelic variants of rs7736074 and rs4975596 modulate TERT expression levels in multiple cancer types, and exhibit preliminary prognostic value for response to cetuximab. |
| RS6220 |
IGF1 |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
RESULTS: The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). |
| RS7736074 |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
We show that allelic variants of rs7736074 and rs4975596 modulate TERT expression levels in multiple cancer types, and exhibit preliminary prognostic value for response to cetuximab. |
| SMAD4 MUTATION |
SMAD4 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, Chinese metastatic colorectal cancer patients harboring either a SMAD4 mutation or NF1 mutation did not respond to treatment with Erbitux (cetuximab) and showed a shorter progression-free survival compared to patients with wild-type SMAD4 or wild-type NF1. |
| SMAD4 MUTATION |
SMAD4 |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective analysis of 65 patients with metastatic colorectal cancer, SMAD4 mutations were more common among patients with no benefit from EGFR-inhibition (cetuximab or panitumumab) (4 patients) than with patients with response to EGFR directed treatment (1 patient). |
| TGFBR1 T204D |
TGFBR1 |
Trastuzumab | Breast Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Treatment with TGF-beta or expression of Alk5(T204D) in HER2-overexpressing cells reduced their sensitivity to the HER2 antibody trastuzumab. |
| TP53 MUTATION |
TP53 |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Avastin (bevacizumab), in combination with chemotherapy, provided a significant survival benefit in patients with colorectal cancers regardless of mutational status in KRAS, BRAF, and TP53. |
| TP53 WILD TYPE |
TP53 |
Capecitabine, Cetuximab, Oxaliplatin | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this retrospective biomarker analysis of the EXPERT-C trial, patients with TP53 wild-type status had a statistically significant better progression free survival (PFS) (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and overall survival (OS) (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) when treated with Cetuximab + CAPOX (Capecitabine, Oxaliplatin) than in the control arm without Cetuximab. |
| UCA1 KNOCKDOWN |
UCA1 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Here, we found that knockdown of the long non-coding RNA, urothelial cancer associated 1 (UCA1), can promote the sensitivity of human breast cancer cells to trastuzumab. Mechanistically, UCA1 knockdown upregulated miR-18a and promoted miR-18a repression of Yes-associated protein 1 (YAP1). These findings demonstrate that the UCA1/miR-18a/YAP1 axis plays an important role in regulating the sensitivity of breast cancer cells to trastuzumab, which has implications for the development of novel approaches to improving breast cancer responses to targeted therapy. |
| VEGFA UNDEREXPRESSION |
VEGFA |
5-fluorouracil, Bevacizumab, Irinotecan, L-Folinic Acid | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Decreased peri- and post-therapeutic expression of VEGFA were significantly associated with response to FOLFIRI plus bevacizumab in 57 patients with metastatic CRC. |
| VEGFD OVEREXPRESSION |
VEGFD |
FOLFIRI Regimen, Ramucirumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Cyramza (ramucirumab) in combination with FOLFIRI chemotherapy improved overall survival (OS) by 2.4 months compared to placebo (13.9 vs 11.5 months) in colorectal cancer patients with high Vegfd level, while resulting in a decrease of OS (12.6 vs 13.1 months) in patients with low Vegfd level. |
| WHRN V400A |
WHRN |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
For cetuximab regimens, patients carrying the GG genotype at DFNB31 rs2274159 or LIFR rs3729740 seemed greater chemosensitive than those carrying at least one A allele (P = 0.025 and P = 0.07). |
| YB-1 S102D |
YB-1 |
Trastuzumab | Breast Carcinoma | Resistant | Preclinical |
Publications Database: ResCur |
Further, to demonstrate the importance of YB-1 in mediating drug resistance, the expression of the active mutant YB-1(S102D) rendered the BT474 cell line insensitive to trastuzumab. |
| YES1 AMPLIFICATION, YES1 OVEREXPRESSION |
YES1 |
Dasatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, dasatinib (Sprycel) treatment of Her2 positive breast cancer cells with YES1 amplification and overexpression restored sensitivity to trastuzumab (Herceptin). |
| YES1 AMPLIFICATION, YES1 OVEREXPRESSION |
YES1 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, amplification and overexpression of Yes1 contributed to trastuzumab (Herceptin) resistance in Her2 positive breast cancer cells, in culture. |