Figure 1.

Main mechanism of action of CDK4/6 inhibitors on cell cycle progression. During early G1 phase, retinoblastoma-associated protein (Rb) is hypophosphorylated, thereby inhibiting the transcription factor E2F and preventing the initiation of DNA replication. Mitogenic signals lead to the expression of cyclin D and subsequent activation of cyclin D-CDK4/6 complexes, which suppresses Rb through phosphorylation and allows E2F to induce G1-S1 transition. CDK4/6 inhibitors halt the cell cycle arrest by inhibiting the activation of the cyclin D-CDK4/6 complexes and all downstream signalling pathways.