Lv et al. review NSCLC cell-cycle dysregulation and report that abnormalities in the cyclin-D–CDK4/6–INK4–RB pathway are common, with preclinical and clinical studies showing encouraging activity of CDK4/6 inhibitors alone or in combinations (pan-NSCLC review; LUAD extrapolation). This evidence concerns the gene CDKN2A and non-small cell lung carcinoma.