In summary, the present study highlights a novel mechanism of palbociclib resistance in KRAS-mutant NSCLC that stems from the ERK-dependent induction of CDK6 and cyclins D1 and D3, as well as increased expression of cyclin E. Increased expression of G1 cyclin-CDK complexes results in part from increased FGFR1 mediated-signaling that is transferable and maintained via bFGF secretion and that causes activation and dependence on a MEK-ERK-mTOR pathway. Here, MAP2K7 is linked to non-small cell lung carcinoma.