Variant-selective and pan-RAS inhibitors enhance targeted agent activity in patient-derived multi-cell type tumor spheroids. (PubMed, Mol Cancer Ther) - Oct 8, 2026 - "As single agents, the KRAS G12C inhibitors elironrasib (RMC-6291) and divarasib, and the KRAS G12D inhibitor MRTX1133, demonstrated variant-selective activity...Daraxonrasib with the MEK inhibitor cobimetinib produced predominantly additive responses with localized Bliss-defined synergy...MRTX1133 combinations reduced viability and produced the highest positive Bliss scores in KRAS G12D models, whereas daraxonrasib exhibited broader activity across RAS genotypes. These findings provide mechanistic support for rational combination strategies targeting convergent RAS effector pathways and inform the design of genotype-directed clinical trials."
Journal • Oncology • Solid Tumor • KRAS
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Beverly A Teicher; Eric M Jones; James H Doroshow; Naoko Takebe; Nathan P Coussens; Thomas S Dexheimer; Thomas Silvers; Zahra Davoudi
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