Application of Cyclin-dependent Kinase 4/6 Inhibitors in the Treatment of Malignancies and the Mechanism of Drug Resistance

Uncontrolled cell proliferation is one of the important hallmarks of malignancies. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors act on CDK4/6 that is over activated by various causes. CDK4/6 inhibitors play anti-tumor roles by restoring normal cell cycle, enhancing anti-tumor immunity, and reforming tumor microenvironment. Currently, CDK4/6 inhibitors have been confirmed to be effective in hormone-receptor-positive breast cancer and were approved as the first-line treatment for this breast cancer in combination with endocrine therapy. Furthermore, CDK4/6 inhibitors have been gradually applied to the treatment of other tumors, but the efficacy remains to be evaluated. Natural or acquired resistance to CDK4/6 inhibitors is a major factor affecting their efficacy. However, at present, only hormone receptor-positive (mainly estrogen receptor-positive) can relatively accurately predict the responsiveness of CDK4/6 inhibitors in combination with endo- crine treatment, and other markers need to be further explored and verified in clinical studies. The mechanism of action, the status of application, and mechanisms of drug-resistance of CDK4/6 inhibitors in the treatment of malignancies were reviewed and summarized in this paper, and the controversy over clinical decision-making on the treatment of breast cancer with CDK4/6 inhibitors was briefly discussed.