Beyond First-Generation KRAS Inhibitors: BBO-8520 Tests the Dual Mechanism Hypothesis

This issue highlights the development of a first-in-class small-molecule covalent KRASG12C inhibitor, BBO-8520, which targets both the active (ON) and inactive (OFF) states of KRAS. This dual-state targeting offers a significant opportunity to overcome the resistance mechanisms that have limited the efficacy of first-generation KRAS inhibitors and addresses critical challenges in KRAS-targeted therapy. See related article by Maciag et al., p. 578.