Targeting Cyclin Dependent Kinase 4/6 for Cancer Therapy

One fundamental hallmark of cancer is uncontrolled cell proliferation. In order to inhibit tumor growth, understanding the mechanisms of disease pathogenesis and the role of cell-cycle regulators which control the division process of cancer cells is necessary, specially CDK4/6, which have been approved as effective therapeutic targets in clinical studies. To date, five CDK4/6 inhibitors have been approved by the U.S. Food and Drug Administration (FDA) and National Medical Products Administration (NMPA). As expected, CDK4/6 inhibitors arrest tumor cells in the G1 phase of the cell cycle. Although undesired, mechanisms of acquired resistance to CDK4/6 inhibitors are beginning to emerge, and extending the use of CDK4/6 inhibitors beyond HR-positive breast cancer is still under consideration and practice. In this assay, we highlight the biological functions of CDK4/6 in the control of cell cycle progression in normal cells and summarize the multiple mechanisms by which the dysregulation of the CDK4/6 pathway of cancer cells. This review also provides a general overview of CDK4/6 inhibitors clinically approved. Instead of monotherapies, combination therapies with CDK inhibitors may especially provide promising results for cancer therapy. We also demonstrate the possible combination with available targeted therapies, immunotherapy, or classical chemotherapy to improve future therapeutic uses of CDK4/6 inhibition in a variety of cancers in clinical trials.