Since CDK4 and CDK6 control key metabolic regulators in physiological and pathological conditions and manipulating metabolic pathways in addition to CDK4/6 inhibition is beneficial in cancer [9,10,11,12], we investigated the metabolic reprogramming that occurs in a panel of isogenic ER+ breast cancer cell lines in response and adaptation to palbociclib. The gene discussed is CDK4; the disease is breast cancer.