EGFR and non-small cell lung carcinoma: In contrast with other targets like EGFR-mutant NSCLC in which a single the T790M mutation is responsible for approximately half of the progressions after first- or second-line specific inhibitors (60), progressions after treatment with KRASG12C inhibitors are caused by both single and combined mechanisms, including: on-target mutations affecting the docking site of this inhibitors; other activating KRAS mutations; activation of the canonical pathways by mutations or activation of upstream and downstream effectors and also activation of non-mutant RAS isoforms.