CDK4 and cancer: The almost synonymous and interchangeable cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), with relatively minor sequence and structural differences, differentially regulate the G1-S phase transition of the cell cycle in CDK4/6 inhibitor (CDK4/6i)-resistant cancer cells, adult tissues, and hematopoietic stem cells (HSCs).[1–5] The crucial question of the molecular mechanisms by which overexpressed CDK6 in cancer resistant cells facilitate cell cycle progression— in lieu of CDK4— remains unanswered.