Gene Variant Detail

Gene KRAS
Variant wild-type
Impact List none
Protein Effect no effect
Gene Variant Descriptions Wild-type KRAS indicates that no mutation has been detected within the KRAS gene.
Associated Drug Resistance

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No Variant Reference Transcript is Available.
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Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF wild-type KRAS wild-type NRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI Phase II Actionable 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% (PMID: 29450468; NCT02295930). 29450468
BRAF wild-type KRAS wild-type NRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI + Bevacizumab Phase II Actionable 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% (PMID: 29450468; NCT02295930). 29450468
FGFR1 dec exp KRAS wild-type lung cancer no benefit Trametinib Preclinical Actionable In a preclinical study, knocking down of Fgfr1 through shRNA did not sensitize KRAS wild-type lung cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
ERBB2 amp KRAS wild-type colorectal cancer no benefit Cetuximab Clinical Study - Cohort Actionable In a retrospective study, 17.6% (3/17) of colorectal cancer patients with wild-type KRAS who did not respond to treatment with either Erbitux (cetuximab) or Vectibix (panitumumab) were found to harbor ERBB2 (HER2) amplifications, while no patients in the KRAS wild-type therapy-responsive cohort were found to have ERBB2 (HER2) amplification or overexpression (n=14) (PMID: 22586653). 22586653
ERBB2 amp KRAS wild-type colorectal cancer no benefit Panitumumab Clinical Study - Cohort Actionable In a retrospective study, 17.6% (3/17) of colorectal cancer patients with wild-type KRAS who did not respond to treatment with either Erbitux (cetuximab) or Vectibix (panitumumab) were found to harbor ERBB2 (HER2) amplifications, while no patients in the KRAS wild-type therapy-responsive cohort were found to have ERBB2 (HER2) amplification or overexpression (n=14) (PMID: 22586653). 22586653
CDKN2A loss KRAS wild-type non-small cell lung carcinoma sensitive Abemaciclib Phase I Actionable In a Phase I trial, a squamous non-small cell lung carcinoma patient with KRAS wild-type and loss of CDKN2A demonstrated a partial response when treated with Abemaciclib (LY2835219) (PMID: 27217383). 27217383
BRAF V600E KRAS wild-type colorectal cancer no benefit Palbociclib + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment did not result in enhanced antitumor activity compared to Ibrance (palbociclib) alone in PDX models of KRAS wild-type colorectal cancer harboring BRAF V600E (PMID: 26369631). 26369631
KRAS wild-type colorectal cancer decreased response AZD4785 Preclinical - Cell culture Actionable In a preclinical study, KRAS wild-type colorectal cancer cell lines demonstrated decreased respond to AZD4785 compared to KRAS mutant cell lines in culture (PMID: 28615361). 28615361
KRAS wild-type Advanced Solid Tumor sensitive GDC-0623 Phase I Actionable In a Phase I trial, GDC-0632 treatment resulted in stable disease for more than 5 months in 13% (6/45) of patients with advanced solid tumors and 1 partial response in a squamous cell vaginal carcinoma patient carrying wild-type KRAS (Mol Cancer Ther 2013;12(11 Suppl):B75). detail...
KRAS wild-type non-small cell lung carcinoma no benefit Selumetinib + Docetaxel Phase II Actionable In a Phase II trial, the combination of Selumetinib (AZD6244) and Taxotere (docetaxel) did not result in a greater clinical benefit in KRAS wild-type patients with non-small cell lung carcinoma when compared to Taxotere (docetaxel) plus placebo (PMID: 29045535; NCT01750281). 29045535
KRAS wild-type non-small cell lung carcinoma no benefit Sorafenib Phase III Actionable In a Phase III trial, Nexavar (sorafenib) treatment in KRAS wild-type non-small cell lung carcinoma patients did not meet its primary endpoint when compared to placebo, resulting in a similar overall survival, however, did meet its secondary endpoint, showing a longer progression free survival (PMID: 26743856). 26743856
KRAS wild-type lung cancer decreased response Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) combination treatment was less efficient at inhibiting proliferation of KRAS wild-type lung cancer cells in culture (PMID: 27338794). 27338794
KRAS wild-type gastric adenocarcinoma sensitive GA201 Preclinical Actionable In a preclinical study, treatment with GA201 induced antibody-dependent cell-mediated cytotoxicity against KRAS wild-type gastric adenocarcinoma in culture, when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
KRAS wild-type biliary tract cancer predicted - sensitive Panitumumab + Gemcitabine + Oxaliplatin Phase II Actionable In a Phase II clinical trial, a PFS difference was not observed between KRAS wild-type biliary tract cancer patients when treated with a combination of Vectibix (panitumumab), Gemzar (gemcitabine), and Eloxatin (oxaliplatin) versus Gemzar (gemcitabine) and Eloxatin (oxaliplatin) only (PMID: 26540314). 26540314
KRAS wild-type colorectal cancer sensitive Rilotumumab + Panitumumab Phase Ib/II Actionable 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 (PMID: 24919569). 24919569
KRAS wild-type colorectal cancer sensitive Bevacizumab Clinical Study Actionable 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 (PMID: 23828442). 23828442
KRAS wild-type colorectal cancer sensitive Bevacizumab Phase III Actionable 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 (PMID: 28632865). 28632865
KRAS wild-type colorectal cancer predicted - sensitive Cetuximab Clinical Study Actionable 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 (PMID: 17998284). 17998284
KRAS wild-type colorectal cancer predicted - sensitive Cetuximab Phase III Actionable 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 (PMID: 28632865). 28632865
KRAS wild-type vaginal squamous tumor sensitive GDC-0623 Phase I Actionable In a Phase I trial, GDC-0632 treatment resulted in stable disease for more than 5 months in 13% (6/45) of patients with advanced solid tumors and 1 partial response in a squamous cell vaginal carcinoma patient carrying wild-type KRAS (Mol Cancer Ther 2013;12(11 Suppl):B75). detail...
KRAS wild-type colorectal cancer predicted - sensitive Napabucasin + Panitumumab Phase Ib/II Actionable 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)). detail...
KRAS wild-type pancreatic cancer decreased response Aphanin Preclinical - Cell culture Actionable In a preclinical study, KRAS wild-type pancreatic cancer cells were less sensitive to Aphanin induced growth inhibition and apoptosis in culture (PMID: 27333990). 27333990
KRAS wild-type colorectal cancer sensitive Panitumumab + Oxaliplatin + Fluorouracil + Irinotecan Phase III Actionable 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 (PMID: 26341920). 26341920
KRAS wild-type colorectal cancer sensitive Panitumumab + Oxaliplatin + Fluorouracil + Irinotecan Phase III Actionable 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 (PMID: 26341920). 26341920
KRAS wild-type colorectal cancer sensitive Panitumumab Phase III Actionable 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). detail...
KRAS wild-type colorectal cancer sensitive Panitumumab FDA approved Actionable 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) (PMID: 18316791; NCT00113763). 18316791
KRAS wild-type colorectal cancer sensitive Panitumumab Phase III Actionable 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 (PMID: 23625191; NCT00113763). 23625191
KRAS wild-type colorectal cancer no benefit SYM004 Phase II Actionable In a Phase II trial, SYM004 treatment did not improve overall survival compared to standard of care in patients with metastatic colorectal cancer harboring no KRAS exon 2 mutations, and acquired resistance to anti-EGFR therapy (PMID: 29423521). 29423521
KRAS wild-type non-small cell lung carcinoma sensitive Erlotinib Phase I Actionable In a Phase I trial, Tarceva (erlotinib) treatment resulted in a greater survival benefit in non-small cell lung cancer patients with wild-type KRAS compared to treatment in those patients harboring KRAS mutations (PMID: 18626007). 18626007
KRAS wild-type colorectal cancer sensitive Panitumumab + cabozantinib Phase Ib/II Actionable 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)). detail...
KRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI Phase III Actionable 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 (PMID: 25605843). 25605843
KRAS wild-type non-small cell lung carcinoma decreased response AZD4785 Preclinical - Pdx Actionable In a preclinical study, AZD4785 inhibited Kras expression in tumors, but had no effect on tumor growth in patient-derived xenograft models of KRAS wild-type non-small cell lung carcinoma (PMID: 28615361). 28615361
KRAS wild-type colorectal adenocarcinoma no benefit Cetuximab + Dasatinib + FOLFOX Phase Ib/II Actionable 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 (PMID: 28280091; NCT00501410). 28280091
KRAS wild-type pancreatic cancer predicted - sensitive Gemcitabine + Refametinib Phase Ib/II Actionable In a Phase I/II trial, Refametinib (BAY86-9766) and Gemzar (gemcitabine) combination treatment resulted in improved overall response rate, disease control rate, progression-free survival, and overall survival (48% vs. 28%, 81% vs. 69%, 8.8 vs. 5.3 months,18.2 vs. 6.6 months, respectively) in pancreatic cancer patients without detectable KRAS mutations in circulating tumor DNA (PMID: 27975152). 27975152
KRAS wild-type colorectal cancer predicted - sensitive Bevacizumab + Capecitabine Phase III Actionable 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)). detail...
KRAS wild-type head and neck squamous cell carcinoma predicted - sensitive Cetuximab + lenalidomide Phase I Actionable In a Phase I trial, Erbitux (cetuximab) and Revlimid (lenalidomide) combination therapy resulted in stable disease in 67% (2/3) of KRAS wild-type head and neck squamous cell cancer patients, and induced Revlimid (lenalidomide) dose-dependent increase of antibody-dependent cellular cytotoxicity (PMID: 27458141). 27458141
KRAS wild-type lung carcinoma decreased response AZD4785 Preclinical - Cell culture Actionable In a preclinical study, KRAS wild-type lung carcinoma cell lines demonstrated decreased respond to AZD4785 compared to KRAS mutant cell lines in culture (PMID: 28615361). 28615361
KRAS wild-type squamous cell carcinoma no benefit Metformin Preclinical - Cell line xenograft Actionable In a preclinical study, Glucophage (metformin) did not induce growth inhibition or apoptosis in a KRAS wild-type squamous cell carcinoma cell line in culture and did not inhibit tumor growth in xenograft models (PMID: 23877793). 23877793
KRAS wild-type colorectal cancer predicted - sensitive Necitumumab + FOLFOX Phase II Actionable In a Phase II clinical trial, the combination of Portrazza (necitumumab) and FOLFOX in colorectal cancer patients resulted in an objective response rate (ORR) of 63.6% (28/44) in the overall intent-to-treat population, with KRAS wild-type patients achieving an ORR of 87.5% (14/16), including complete response in 25% (4/16), and partial response in 62.5% (10/16) of patients (PMID: 26766738). 26766738
KRAS wild-type colorectal cancer predicted - sensitive Cetuximab + lenalidomide Phase I Actionable 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 (PMID: 27458141). 27458141
ERBB2 positive KRAS wild-type colorectal cancer sensitive Trastuzumab + Lapatinib Phase II Actionable In a Phase II clinical trial, 30% (8/27) of patients with ERBB2 (HER2)-positive KRAS wild-type colorectal cancer achieved an objective response and 44% (12/27) of patients had stable disease when treated with the combination of Herceptin (trastuzumab) and Tykerb (lapatinib) (PMID: 27108243). 27108243
AKT1 E17K KRAS wild-type BRAF wild-type colorectal cancer resistant Cetuximab + Irinotecan Clinical Study Actionable 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) (PMID: 25714871). 25714871
BRAF wild-type KRAS wild-type non-small cell lung carcinoma predicted - sensitive BMS-906024 + Paclitaxel Preclinical - Pdx & cell culture Actionable In a preclinical study, combination of BMS-906024 and Taxol (paclitaxel) resulted in synergy in BRAF and KRAS wild-type non-small cell lung cancer (NSCLC) cell lines in culture, but not in cell lines harboring KRAS or BRAF activating mutations, and demonstrated enhanced tumor growth inhibition in cell line and patient-derived xenograft (PDX) models of BRAF, KRAS wild-type NSCLC (PMID: 28978720). 28978720
BRAF wild-type KRAS wild-type colorectal cancer decreased response LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 demonstrated limited efficacy in BRAF and KRAS wild-type patient-derived xenograft models of colorectal cancer, resulted in a disease control rate of 3.8% (1/26) (PMID: 28611205). 28611205