We further delineate that autophagy protects from PLK1/FGFR1 inhibitor cytotoxicity and that antagonizing the compensation mechanism by clinically approved chloroquine fully realizes the therapeutic potential of PLK1 and FGFR1 targeting therapy, producing potent and durable responses in KRAS‐mutant patient‐derived xenografts and a genetically engineered mouse model of Kras‐induced lung adenocarcinoma. Here, KRAS is linked to lung adenocarcinoma.