Fig. 2.

The mechanistic insight of CDK4/6 inhibitors in the management of breast cancer. CDK4/6 activation leads to Rb activation via phosphorylation. Activated Rb enables cell cycle progression by turning on E2F transcription. In addition, CDK4 and CDK6 endorse the stabilization and activation of FOXM1 via phosphorylation, which in turn promotes the upregulation of the G1/S phase genes and the avoidance of cell senescence. CDK4/6 inhibitors, such as palbociclib, ribociclib, or abemaciclib arrest the cell cycle by suppressing CDK4/6 downstream signaling event and arrest. Grey arrows represent downstream events and red lines represent inhibition. CDK, Cyclin-dependent kinase; FOXM1, Forkhead box protein M1; Rb: Retinoblastoma-associated protein