So far, the reported efficacies of KRAS G12C inhibitors monotherapy-exemplified by agents such as sotorasib, adagrasib, and divarasib-were less impressive in KRAS G12C-mutated CRC than those in NSCLC, with reported objective response rates (ORR) ranging from 9.7% to 29.1% and median progression-free survival (PFS) from 4 to 5.6 months.10–12 This intertumoral disparity suggests the involvement of CRC-specific resistance mechanisms, which is potentially driven by compensatory pathway activation. The gene discussed is KRAS; the disease is colorectal carcinoma.