CDK4/6 inhibitor resistance mechanisms and treatment strategies (Review)

Abstract

In recent years, the incidence rate of breast cancer has increased year by year, and it has become a major threat to the health of women globally. Among all breast cancer subtypes, the hormone receptor (HR) epidermal growth factor receptor 2 (HER2)- luminal subtype breast cancer is the most common form of breast cancer. Cyclin-dependent kinase 4 and 6 (CD K4/6) inhibitors, the hotspots in the field of targeted therapy for breast cancer, have proved to exhibit a good effect on patients with HR breast cancer in a number of clinical trials, but the problem of drug resistance is inevitable. At present, three specific CD K4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have been approved by the USA Food and Drug Administration for the first-line treatment of HR breast cancer. The drug resistance mechanisms of CD K4/6 inhibitors can be divided into cell cycle-specific resistance and cell cycle non-specific resistance. With the discovery of the drug resistance mechanism of CD K4/6 inhibitors, various targeted strategies have been proposed. The present review mainly discusses the mechanism of CD K4/6 inhibitors, drug resistance mechanisms and treatment strategies after resistance.