Cyclin-dependent kinase 4 and 6 (CDK4/6)

Cyclin-dependent kinase 4 and 6 (CDK4/6) are essential serine/threonine kinases that govern the transition of cells from the G1 phase to the S phase of the cell cycle [1, 6, 10]. These kinases associate with D-type cyclins to form active complexes that phosphorylate the retinoblastoma (Rb) protein, a critical tumor suppressor [2, 7, 13]. Phosphorylation of Rb leads to the release of E2F transcription factors, which activate the genetic program necessary for DNA synthesis and cell division [7, 13, 16]. In many cancers, especially hormone receptor-positive (HR+) breast cancer, the CDK4/6-cyclin D-Rb axis is hyperactivated, promoting uncontrolled tumor growth [8, 14, 15]. Selective CDK4/6 inhibitors, such as palbociclib, bind to the ATP-binding site of these kinases, preventing Rb phosphorylation and effectively halting the cell cycle in the G1 phase [2, 4, 5]. While these therapies have revolutionized the treatment of advanced breast cancer, they require careful monitoring for hematologic toxicities, most notably neutropenia, which results from the inhibition of CDK6 in bone marrow progenitor cells [12, 18, 20].

Other names

Cyclin-dependent kinase 4Cyclin-dependent kinase 6CDK4CDK6Cell division protein kinase 4Cell division protein kinase 6PSK-J3PLSTIRECMM3MCPH12

Selective inhibition of CDK4 and CDK6 kinases, preventing phosphorylation of the retinoblastoma (Rb) protein and causing G1-phase cell cycle arrest.