Expanding the RAS-verse: Novel Inhibitors, Emergent Dependencies, Fresh Opportunities in RAS -Mutant NSCLC

In this issue, two studies establish KRASG13C as a directly targetable oncoprotein in non-small cell lung cancer (NSCLC) while revealing distinct dependence of codon 13-mutant NSCLC on wild-type (WT) RAS and enhanced sensitivity to standard-of-care chemotherapy. A third study highlights rewired oncogenic signaling through WT RAS as a therapeutically tractable mechanism of resistance to KRASG12C inhibitors in the context of acquired oncogenic kinase fusions. See related article by Scaparone et al., p. 2242 See related article by Seamon et al., p. 2256 See related article by McDaid et al., p. 2274.