{"entity":{"id":"kras-mutation-subtypes","kind":"term","name":"KRAS mutation subtypes (G12C, G12D, G12V)","aka":["G12C","G12D","G12V","G12R","G13D","Q61H","KRAS G12C","KRAS G12D","KRAS-mutant","KRAS-mutated","KRAS mutation","KRAS mutations","RAS-mutant","RAS mutation","RAS-mutated","non-G12C","pan-RAS","pan-KRAS","RAS(ON)","RAS(OFF)","RAS mutations"],"tldr":"KRAS, the most commonly mutated cancer gene, comes in flavours named by the exact amino acid change. G12C (common in smokers' lung cancer) was the first to get a drug; G12D dominates pancreatic and colorectal cancer and its inhibitors are arriving now.","summary":"KRAS is mutated in about 90% of pancreatic, 40% of colorectal and 30% of lung adenocarcinomas. The G12C variant (13% of lung adenocarcinoma) is targeted by sotorasib and adagrasib, approved in 2021-22 with modest durability; G12D (40% of pancreatic cancer) is the target of zoldonrasib and others; daraxonrasib and related RAS(ON) multi-selective inhibitors cover several variants and produced the first positive phase 3 in pancreatic cancer. Variant also predicts behaviour: G12C lung tumours are smoking-related and immunogenic, while colorectal KRAS mutations of any type preclude EGFR antibodies. Co-mutations (STK11, KEAP1, TP53) modify prognosis and immunotherapy benefit.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/KRAS","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/KRAS"}],"tags":[],"related":["driver-mutation","wild-type","stk11-keap1"],"cancers":["nsclc","pancreatic","colorectal"],"sections":["targeted-therapy"],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["sotorasib","adagrasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/kras-mutation-subtypes/","neighbours":{"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"kras-allelic-imbalance","kind":"term","name":"KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer","route":"/terms/kras-allelic-imbalance/"},{"id":"pancreatic-trials-open-today","kind":"term","name":"Pancreatic cancer trials open today (registry snapshot and UK sites)","route":"/terms/pancreatic-trials-open-today/"},{"id":"stk11-keap1","kind":"term","name":"STK11 / KEAP1 co-mutations","route":"/terms/stk11-keap1/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"kras-g12c-nsclc","kind":"cancer","name":"KRAS G12C-mutant non-small-cell lung cancer","route":"/cancers/kras-g12c-nsclc/"},{"id":"kras-g12c-pdac","kind":"cancer","name":"KRAS G12C-mutant pancreatic ductal adenocarcinoma","route":"/cancers/kras-g12c-pdac/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"drug":[{"id":"adagrasib","kind":"drug","name":"Adagrasib","route":"/drugs/adagrasib/"},{"id":"fulzerasib","kind":"drug","name":"Fulzerasib","route":"/drugs/fulzerasib/"},{"id":"garsorasib","kind":"drug","name":"Garsorasib","route":"/drugs/garsorasib/"},{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/"}],"paper":[{"id":"paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018","kind":"paper","name":"Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma","route":"/key-papers/paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018/"},{"id":"paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015","kind":"paper","name":"Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities","route":"/key-papers/paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015/"},{"id":"paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023","kind":"paper","name":"CodeBreaK 100: sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer","route":"/key-papers/paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023/"},{"id":"paper-daraxonrasib-pancreatic-n-engl-j-med-2026","kind":"paper","name":"Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer","route":"/key-papers/paper-daraxonrasib-pancreatic-n-engl-j-med-2026/"},{"id":"paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022","kind":"paper","name":"Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status","route":"/key-papers/paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022/"},{"id":"paper-arbour-kras-co-mutation-outcomes-ccr-2018","kind":"paper","name":"Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer","route":"/key-papers/paper-arbour-kras-co-mutation-outcomes-ccr-2018/"},{"id":"paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016","kind":"paper","name":"KRAS G12D mutation subtype is a prognostic factor for advanced pancreatic adenocarcinoma","route":"/key-papers/paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016/"},{"id":"paper-almoguera-kras-codon-12-pancreatic-cell-1988","kind":"paper","name":"Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes","route":"/key-papers/paper-almoguera-kras-codon-12-pancreatic-cell-1988/"},{"id":"paper-alexandrov-tobacco-smoking-mutational-signatures-science-2016","kind":"paper","name":"Mutational signatures associated with tobacco smoking in human cancer","route":"/key-papers/paper-alexandrov-tobacco-smoking-mutational-signatures-science-2016/"},{"id":"paper-witkiewicz-pancreatic-exomes-utsw-nat-commun-2015","kind":"paper","name":"Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets","route":"/key-papers/paper-witkiewicz-pancreatic-exomes-utsw-nat-commun-2015/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"idea":[{"id":"idea-pdac-ras-inhibitor-combinations-and-sequencing","kind":"idea","name":"RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression","route":"/ideas/idea-pdac-ras-inhibitor-combinations-and-sequencing/"}],"trial":[{"id":"codebreak-100","kind":"trial","name":"CodeBreaK 100 (pancreatic cancer cohort)","route":"/trials/codebreak-100/"},{"id":"nct03785249","kind":"trial","name":"Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1","route":"/trials/nct03785249/"},{"id":"nct05737706","kind":"trial","name":"Study of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation","route":"/trials/nct05737706/"},{"id":"nct05379985","kind":"trial","name":"Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS","route":"/trials/nct05379985/"},{"id":"nct07805954","kind":"trial","name":"Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mut","route":"/trials/nct07805954/"},{"id":"nct07621718","kind":"trial","name":"Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-muta","route":"/trials/nct07621718/"}],"biomarker":[{"id":"kras-g12c","kind":"biomarker","name":"KRAS G12C","route":"/biomarkers/kras-g12c/"},{"id":"kras-g12d","kind":"biomarker","name":"KRAS G12D (and other non-G12C KRAS mutations)","route":"/biomarkers/kras-g12d/"},{"id":"stk11-keap1-loss","kind":"biomarker","name":"STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma","route":"/biomarkers/stk11-keap1-loss/"}]}}