{"entity":{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","aka":[],"tldr":"Drugs against the most common cancer gene, considered impossible to target until sotorasib in 2021.","summary":"Covalent G12C inhibitors (sotorasib, adagrasib, divarasib, olomorasib) work in NSCLC and, with cetuximab, in colorectal cancer. Non-covalent G12D inhibitors (zoldonrasib, MRTX1133) and pan-RAS(ON) tri-complex inhibitors (daraxonrasib RMC-6236, in phase 3 RASolute 302 in second-line pancreatic cancer) aim at pancreatic cancer, where KRAS is near-universal. Degraders and vaccines (ELI-002) follow.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/KRAS","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/KRAS"}],"tags":[],"related":[],"cancers":["nsclc","colorectal","pancreatic"],"sections":["targeted-therapy"],"technologies":[],"targets":["kras","egfr"],"drugs":["sotorasib","adagrasib","daraxonrasib"],"companies":["amgen","bms","revolution-medicines","bridgebio-oncology-therapeutics","erasca","kumquat-biosciences","treeline-biosciences"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023","paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023","paper-daraxonrasib-pancreatic-n-engl-j-med-2026","paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016"],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer biomarkers: the covalent G12C inhibitors reach only the 1 to 2% with that allele (21 to 33% response; Strickler 2023, Bekaii-Saab 2023), whereas the tri-complex RAS(ON) inhibitors address the G12D, G12V, G12R and Q61 alleles that make up the rest, with daraxonrasib giving overall survival 13.2 against 6.6 months in previously treated RAS G12-mutant disease (O'Reilly 2026). Allele-level reporting therefore matters: G12D is both the commonest and the worst-prognosis allele (Bournet 2016)."],"principle":"Inhibitors bind covalently to the mutant cysteine in the switch-II pocket (G12C), or form a cyclophilin-A-mediated tri-complex that blocks effector binding (RAS(ON) inhibitors).","strengths":["First drugs for a 40-year-old target"],"limitations":["Modest durability as monotherapy","Adaptive RTK feedback requires combinations"],"since":2021},"route":"/technologies/kras-inhibitors/","neighbours":{"cancer":[{"id":"borderline-resectable-pdac","kind":"cancer","name":"Borderline resectable pancreatic ductal adenocarcinoma","route":"/cancers/borderline-resectable-pdac/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"kras-g12c-colorectal","kind":"cancer","name":"KRAS G12C-mutant colorectal cancer","route":"/cancers/kras-g12c-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":"locally-advanced-pdac","kind":"cancer","name":"Locally advanced unresectable pancreatic ductal adenocarcinoma","route":"/cancers/locally-advanced-pdac/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"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/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"nras","kind":"target","name":"NRAS","route":"/targets/nras/"},{"id":"shp2","kind":"target","name":"SHP2 (PTPN11)","route":"/targets/shp2/"}],"drug":[{"id":"adagrasib","kind":"drug","name":"Adagrasib","route":"/drugs/adagrasib/"},{"id":"daraxonrasib","kind":"drug","name":"Daraxonrasib","route":"/drugs/daraxonrasib/"},{"id":"divarasib","kind":"drug","name":"Divarasib","route":"/drugs/divarasib/"},{"id":"elironrasib","kind":"drug","name":"Elironrasib","route":"/drugs/elironrasib/"},{"id":"fulzerasib","kind":"drug","name":"Fulzerasib","route":"/drugs/fulzerasib/"},{"id":"garsorasib","kind":"drug","name":"Garsorasib","route":"/drugs/garsorasib/"},{"id":"glecirasib","kind":"drug","name":"Glecirasib","route":"/drugs/glecirasib/"},{"id":"mrtx1133","kind":"drug","name":"MRTX1133","route":"/drugs/mrtx1133/"},{"id":"olomorasib","kind":"drug","name":"Olomorasib","route":"/drugs/olomorasib/"},{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/"},{"id":"zoldonrasib","kind":"drug","name":"Zoldonrasib","route":"/drugs/zoldonrasib/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"},{"id":"bridgebio-oncology-therapeutics","kind":"company","name":"BridgeBio 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Biosciences","route":"/companies/treeline-biosciences/"},{"id":"verastem","kind":"company","name":"Verastem Oncology","route":"/companies/verastem/"}],"paper":[{"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-codebreak-200-lancet-2023","kind":"paper","name":"CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug","route":"/key-papers/paper-codebreak-200-lancet-2023/"},{"id":"paper-codebreak-300-nejm-2023","kind":"paper","name":"CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer","route":"/key-papers/paper-codebreak-300-nejm-2023/"},{"id":"paper-holderfield-ras-on-multi-selective-inhibitor-nature-2024","kind":"paper","name":"Concurrent inhibition of oncogenic and 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