Gene

KRAS

KRas proto-oncogene, GTPase

Explore in graph →CI-GENE-00007164HGNC:6407 ENSG00000133703 NCBI 3845 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (525)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 101–150 of 525 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
KRAS G12A9
Melphalan	Multiple Myeloma	Predictive	D	Supports Resistance	2	accepted	EID2013 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso…

Cohorts

Alteration frequency by cohort (200)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved200 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Lung Adenocarcinoma (TCGA, Firehose Legacy) luad_tcga	Lung Adenocarcinoma	Ssm	75	230	32.6%

Literature

Linked publications (113)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 113 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
· N Engl J Med · 2008 · PMID 18946061 · validated civic_curation pubmed
Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial.
· JAMA · 2017 · PMID 28492898 · validated civic_curation pubmed
Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.
· J Natl Compr Canc Netw · 2017 · PMID 28275037 · validated civic_curation pubmed
Sotorasib for Lung Cancers with KRAS p.G12C Mutation.
· N Engl J Med · 2021 · PMID 34096690 · validated civic_curation

KRAS G12C41
(prognostic)	Lung Non-Small Cell CarcinomaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	accepted	EID1217 In a study of 48 NSCLC patients, those with G12C or G12V mutant KRAS were associated with decreased progression free survival (1.84 months) compared with other KRAS mutants or with wild-type KRAS (3.3… (full text at CIViC) PMID 22247021 · Ihle et al., 2012 · Open in CIViC	civic
(diagnostic)	Malignant Lung Neoplasm	Diagnostic	B	Supports Positive	2	accepted	EID227 KRAS G12C occur more frequently in women than men. PMID 23014527 · Dogan et al., 2012 · Open in CIViC	civic
Adagrasib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	submitted	EID13009 In the phase II cohort of the KRYSTAL-1 trial, 112 evaluable patients with previously treated advanced KRASG12C-mutated NSCLC were treated with adagrasib monotherapy (600-mg in capsule form twice dail… (full text at CIViC) PMID 35658005 · Jänne et al., 2022 · Open in CIViC	civic
〃	Solid NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID7572 In cell lines, MRTX849 inhibits growth and viability of cells harboring KRAS G12C mutations, but not in cells with other mutant forms or of wild-type KRAS. In animal models, MRTX849 demonstrates anti… (full text at CIViC) Open in CIViC	civic
Adagrasib + CetuximabCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID12063 The efficacy of adagrasib + cetuximab combination therapy was tested in 94 patients harbouring colorectal cancers with KRAS G12C mutations. ORR was used as the primary end-point for the study. The ORR… (full text at CIViC) PMID 38587856 · Yaeger et al., 2024 · Open in CIViC	civic
ARS-1620	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	submitted	EID5927 in a PDX model of NSCLC G12C-mutant KRAS, this mutation can be selectively targeted by ARS-1620, which represents a new generation of KRASG12C-specific inhibitors. PMID 29373830 · Janes et al., 2018 · Open in CIViC	civic
ARS-1620 + Sotorasib + VociprotafibCombination	Malignant NeoplasmALIAS	Predictive	D	Supports N/A	3	submitted	EID8039 The resistance to novel drugs targeting the G12C KRAS variant is caused by RAS pathway reactivation. Ryan et al showed that SHP2, which delivers signals from RTKs to RAS, is critical for RAS pathway a… (full text at CIViC) PMID 31776128 · Ryan et al., 2020 · Open in CIViC	civic
ARS-853 + Epidermal Growth Factor Receptor Tyrosine Kinase InhibitorCombination	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	accepted	EID1173 Preclinical study to investigate mechanisms of KRAS G12C activity and inhibition with ARS-853, a covalent (irreversible) inhibitor which binds KRAS G12C in the GDP-bound state to prevent activation. R… (full text at CIViC) PMID 26739882 · Patricelli et al., 2016 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3962 In a retrospective study of 30 metastatic colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=13) treated with cetuximab and standard chemotherapy were associated with an absen… (full text at CIViC) PMID 16618717 · Lièvre et al., 2006 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3963 In a retrospective study of 113 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation treated with cetuximab plus irinotecan (34/83) were associated… (full text at CIViC) PMID 17998284 · De Roock et al., 2008 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	rejected	EID3964 In a retrospective study of 168 metastatic colorectal cancer patients, patients with a KRAS exon 2 mutation (32/92) treated with cetuximab as salvage therapy (second-line therapy or higher) in combina… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3965 In a retrospective study of 59 metastatic, chemotherapy-refractory, colorectal cancer patients, patients with a KRAS exon 2 mutation (n=22) treated with cetuximab and standard chemotherapy were assoc… (full text at CIViC) PMID 17375050 · Di Fiore et al., 2007 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3966 In a retrospective study of 89 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=24) treated with cetuximab plus chemotherapy were associated… (full text at CIViC) PMID 18202412 · Lièvre et al., 2008 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3968 In a retrospective study of 572 advanced colorectal cancer patients, patients treated with cetuximab and best supportive care with a KRAS exon 2 mutation (81/164) were associated with reduced response… (full text at CIViC) PMID 18946061 · Karapetis et al., 2008 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3969 In a phase 3 clinical study of 1,198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI were associated with reduced overal… (full text at CIViC) PMID 21502544 · Van Cutsem et al., 2011 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3970 In a phase 2 clinical study of 344 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFOX-4 (n=52) were associated with reduced … (full text at CIViC) PMID 19114683 · Bokemeyer et al., 2009 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3971 In a retrospective study of 95 metastatic colorectal cancer patients, patients harboring KRAS activating mutation (n=33) and treated with cetuximab plus standard chemotherapy were reportedly non-respo… (full text at CIViC) PMID 20010090 · Yen et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3972 In a phase 3 clinical study (NCT00154102) of 1198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI (n=105) were associate… (full text at CIViC) PMID 19339720 · Van Cutsem et al., 2009 · Open in CIViC	civic
〃	Malignant Colon Neoplasm	Predictive	C	Supports Resistance	—	submitted	EID3981 In a phase 3 clinical study,�BRAF wild-type stage III colon cancer patients harboring KRAS G12C mutation (n=82) and treated with cetuximab plus standard chemotherapy were associated with decreased dis… (full text at CIViC) PMID 24687927 · Yoon et al., 2014 · Open in CIViC	civic
Cetuximab + ChemotherapyCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	accepted	EID3967 This was a retrospective study of 691 cetuximab treated patients with metastatic, chemotherapy refractory colorectal cancer. Of those, 16 patients harbored KRAS G12C, were BRAF, NRAS and PIK3CA wt, an… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3980 In a non-small cell lung cancer patient with an ALK gene rearrangement and a KRAS G12C co-mutation, KRAS G12C was reported to be resistant to crizotinib treatment. In an in vitro study, a CUTO-1 cell … (full text at CIViC) PMID 22235099 · Doebele et al., 2012 · Open in CIViC	civic
〃	Lung Adenocarcinoma	Predictive	C	Supports Resistance	—	submitted	EID3983 In two lung adenocarcinoma patients with EML4-ALK rearrangement (known to be sensitizing to crizotinib) and KRAS G12C co-mutation, progressive disease in response to 2nd-line crizotinib monotherapy wa… (full text at CIViC) PMID 26712101 · Ulivi et al., 2016 · Open in CIViC	civic
Dactolisib + SelumetinibCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID2212 In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring BRAF, KRAS, NRAS or PIK3CA mutations and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
Divarasib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	accepted	EID11652 A phase 1 clinical study conducted with Divarasib in a total of 137 patients, of which 60 patients had NSCLC with G12C mutation in the KRAS gene. Confirmed response was noted in 53.4% (95% CI; 39.9 to… (full text at CIViC) PMID 37611121 · Sacher et al., 2023 · Open in CIViC	civic
Docetaxel + SelumetinibCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	accepted	EID1142 83 patients from a phase II trial (docetaxel + placebo or MEK1/2 inhibitor selumetinib) with KRAS mutant tumors were retrospectively assessed for differences in OS, PFS, ORR and change in tumor size a… (full text at CIViC) PMID 26125448 · Jänne et al., 2015 · Open in CIViC	civic
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3976 In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3977 In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC	civic
Gefitinib	Malignant Lung Neoplasm	Predictive	B	Supports Resistance	2	accepted	EID2257 In recurrent lung cancer patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib, patients with KRAS mutations had a lower frequency of partial response (PR) and… (full text at CIViC) PMID 17409929 · Endoh et al., 2006 · Open in CIViC	civic
Erlotinib + GefitinibSubstitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	accepted	EID1216 In a study of 448 metastatic colorectal cancer patients treated with EGFR-TKIs and tested for EGFR and KRAS mutations, 69 tested positive for KRAS mutations. In 38 EGFR wildtype patients treated with … (full text at CIViC) PMID 23313110 · Fiala et al., 2013 · Open in CIViC	civic
Melphalan	Multiple Myeloma	Predictive	B	Supports Resistance	2	rejected	EID2258 In a study of patients receiving melphalan-based therapy, those with KRAS codon 12 mutations were less likely to have a positive response than those with wildtype KRAS (26.9% vs. 58.3%, P=0.015). PMID 19284554 · Greco et al., 2009 · Open in CIViC	civic
〃	Multiple Myeloma	Predictive	B	Supports Resistance	—	submitted	EID2259 Activating mutations in KRAS or NRAS were observed more frequently in multiple myeloma patients than in patients with monoclonal gammopathy of uncertain significance (MGUS) (31% vs. 5% ). Another stu… (full text at CIViC) PMID 11524732 · Bezieau et al., 2001 · Open in CIViC	civic
〃	Multiple Myeloma	Predictive	B	Supports Resistance	—	submitted	EID2260 Activating mutations in KRAS or NRAS were observed more frequently in multiple myeloma patients than in patients with monoclonal gammopathy of uncertain significance (MGUS) (31% vs. 5% ). Another stu… (full text at CIViC) PMID 15339850 · Rasmussen et al., 2005 · Open in CIViC	civic
〃	Multiple Myeloma	Predictive	D	Supports Resistance	2	accepted	EID2261 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 11050000 · Rowley et al., 2000 · Open in CIViC	civic
〃	Multiple Myeloma	Predictive	D	Supports Resistance	2	accepted	EID2263 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 16497971 · Hoang et al., 2006 · Open in CIViC	civic
〃	Multiple Myeloma	Predictive	D	Supports Resistance	—	accepted	EID2262 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 12483530 · Rowley et al., 2002 · Open in CIViC	civic
Palbociclib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID3975 In an in vitro study, SW837 cell line expressing KRAS G12C mutation were associated with sensitivity to palbociclib treatment as compared to cells treated with DMSO control. Sensitivity was determine… (full text at CIViC) PMID 27167191 · Lee et al., 2016 · Open in CIViC	civic
Panitumumab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	3	accepted	EID2253 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… (full text at CIViC) PMID 18316791 · Amado et al., 2008 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID2254 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 16953233 · Oliveira et al., 2007 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID2255 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 2547513 · Bos, 1989 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID2256 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 8462792 · Benhattar et al., 1993 · Open in CIViC	civic
Pan-RAF/MEK Molecular Glue NST-628 + SotorasibCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	submitted	EID13158 In KRAS G12C-mutant NCI-H23 tumor models, NST-628 enhanced the activity of KRAS G12C inhibition. In vivo, NST-628 at 2 mg/kg once daily or sotorasib at 100 mg/kg once daily slowed NCI-H23 tumor growth… (full text at CIViC) PMID 38588399 · Ryan et al., 2024 · Open in CIViC	civic

KRAS G12C41

(prognostic)

Lung Non-Small Cell CarcinomaCURATED_BROADER

Prognostic

Supports Poor Outcome

accepted

EID1217

In a study of 48 NSCLC patients, those with G12C or G12V mutant KRAS were associated with decreased progression free survival (1.84 months) compared with other KRAS mutants or with wild-type KRAS (3.3… (full text at CIViC)

PMID 22247021 · Ihle et al., 2012 · Open in CIViC