Agents directly targeting KRAS-G12C have limited activity against KRASG12C-mutant CRC in part because of EGFR-mediated reactivation of extracellular signal-regulated kinase (ERK) signaling, leading to combination trials with agents directed against KRAS-G12C and EGFR (ref. 33). The gene discussed is EGFR; the disease is colorectal carcinoma.