KRAS and neoplasm: The use of structure-guided design and optimization approaches led to the development of RMC-7977, the first orally bioavailable, multiselective, pan-KRAS-mutant GTP-bound inhibitor.315 Preclinically, RMC-7977 has demonstrated potent activity against RAS-addicted tumors with various RAS genotypes, particularly against KRASG12 mutations: treatment with RMC-7977 led to tumor regression across diverse preclinical models, including those resistant to KRASG12C inhibitors.315 This RAS-ON, a multiselective inhibitor, could target multiple oncogenic and wild-type RAS isoforms.