CDK4: a master regulator of the cell cycle and its role in cancer

The cell cycle is regulated in part by cyclins and their associated serine/threonine cyclin-dependent kinases, or CDKs. CDK4, in conjunction with the D-type cyclins, mediates progression through the G(1) phase when the cell prepares to initiate DNA synthesis. Although Cdk4-null mutant mice are viable and cell proliferation is not significantly affected in vitro due to compensatory roles played by other CDKs, this gene plays a key role in mammalian development and cancer. This review discusses the role that CDK4 plays in cell cycle control, normal development and tumorigenesis as well as the current status and utility of approved small molecule CDK4/6 inhibitors that are currently being used as cancer therapeutics.