Rationale for RAS Mutation-Tailored Therapies

RAS mutations are among the most common genetic alterations found in cancerous tumors but rational criteria or strategies for targeting RAS-dependent tumors are only recently emerging. Clinical and laboratory data suggest that patient selection based on specific RAS mutations will be an essential component of these strategies. A thorough understanding of the biochemical and structural properties of mutant RAS proteins form the theoretical basis for these approaches. Direct inhibition of KRAS G12C by covalent inhibitors is a notable recent example of the RAS mutation-tailored approach that establishes a paradigm for other RAS mutation-centered strategies.