{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Skoulidis F"],"funding":["NCI NIH HHS","Amgen Inc."],"pagination":["2755-2767"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12353874"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(8)"],"pubmed_abstract":["Molecular determinants of KRAS(G12C)inhibitor efficacy in KRAS<sup>G12C</sup>-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized. Here we report one of the largest integrated analyses to date of sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 studies. We reveal differential sotorasib activity and relative benefit compared to docetaxel across KRAS<sup>G12C</sup>-mutated NSCLC co-mutational subsets and transcriptional subtypes. We also identify low expression of TTF1 and KEAP1 co-mutations/NRF2 activation as major determinants of sotorasib anti-tumor efficacy and adverse prognostic features. Exploratory analyses highlight potential tumor cell-extrinsic contributors to sotorasib anti-tumor activity and suggest that early on-t"],"journal":["Nature medicine"],"pubmed_title":["Molecular determinants of sotorasib clinical efficacy in KRAS&lt;sup&gt;G12C&lt;/sup&gt;-mutated non-small-cell lung cancer."],"pmcid":["PMC12353874"],"funding_grant_id":["P30 CA008748"],"pubmed_authors":["Couraud S","Kim SW","Lena H","Dooms C","Lindsay CR","Paz-Ares Rodriguez L","Toyozawa R","Mountzios G","Skoulidis F","Wolf J","Chmielewska I","Mukundan L","Dy GK","Nadal E","Velcheti V","Hindoyan A","Anderson A","Hong DS","Li BT","Tomasini P","Wilmanski T","van der Wekken AJ","Reddy A","Curioni Fontecedro A","de Langen AJ","Mehta B","Sacher A","Pati A","Rocco D","Ardito-Abraham C","Schuler M","O'Byrne K"],"additional_accession":[]},"is_claimable":false,"name":"Molecular determinants of sotorasib clinical efficacy in KRAS&lt;sup&gt;G12C&lt;/sup&gt;-mutated non-small-cell lung cancer.","description":"Molecular determinants of KRAS(G12C)inhibitor efficacy in KRAS<sup>G12C</sup>-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized. Here we report one of the largest integrated analyses to date of sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 studies. We reveal differential sotorasib activity and relative benefit compared to docetaxel across KRAS<sup>G12C</sup>-mutated NSCLC co-mutational subsets and transcriptional subtypes. We also identify low expression of TTF1 and KEAP1 co-mutations/NRF2 activation as major determinants of sotorasib anti-tumor efficacy and adverse prognostic features. Exploratory analyses highlight potential tumor cell-extrinsic contributors to sotorasib anti-tumor activity and suggest that early on-t","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-29T15:07:28.504Z","creation":"2026-04-08T05:10:49.098Z"},"accession":"S-EPMC12353874","cross_references":{"pubmed":["40437272"],"doi":["10.1038/s41591-025-03732-5"]}}