CDK4 and cancer: As RB1 inactivation is a genomic driver of resistance to several targeted therapies, including AR antagonists (5–7), ER antagonists (8, 9), CDK4/6 inhibitors (10), and EGFR tyrosine kinase inhibitors (11) and it predicts poor clinical outcomes across cancer types (52), our study provide a solution to the pressing need for more effective treatment of RB1-deficient malignancies.