In KRAS-mutant non-small cell lung cancer (NSCLC) treated with trametinib, Manchado et al. demonstrated a compensatory increase in fibroblast growth factor receptor 1 (FGFR1) causing adaptive drug resistance, which when abrogated genetically or pharmacologically, resulted in apparent synthetic lethality and dramatic therapeutic response in vitro and in vivo. Here, KRAS is linked to non-small cell lung carcinoma.