RAF1 S257L/S259F hotspot mutations: functional characterization and intrinsic resistance to the RAS(ON) inhibitor daraxonrasib in melanoma
These findings establish RAF1 S257L/S259F as critical determinants of MAPK pathway activation and cellular response under daraxonrasib, provide mechanistic insights into intrinsic resistance to RAS(ON) inhibition, and underscore a therapeutic framework for genotype-guided combination strategies in RAF1-mutant melanoma.