Cyclin-dependent kinase (CDK) 4/6 inhibition has been demonstrated to improve progression-free survival (PFS) in patients with human epidermal growth factor receptor 2 (HER2−), hormone receptor positive (HR+) in advanced breast cancer [1–3]. Palbociclib, ribociclib and abemaciclib are orally bioavailable selective CDK 4/6 inhibitors. These small molecules likely bind the ATP-binding pocket within the CDK4/6 protein kinases thereby inhibiting phosphorylation of retinoblastoma tumour suppressor protein (Rb). In its hypophosphorylated state Rb remains bound to E2F thereby preventing progression through the G1-S-cell cycle checkpoint [4]. The mechanism behind the observed efficacy of CDK inhibition in metastatic breast cancer may relate to a dependence of HR+ breast cancer on CDK4/6 activity to override Rb mediated repression of cell cycle progression (Figure 1) [5]
