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) + /human epidermal growth factor receptor 2 (HER2)luminal subtype breast cancer is the most common form of breast cancer. cyclin-dependent kinase 4 and 6 (cdK4/6) inhibitors, the hotspots in the field of targeted therapy for breast cancer, have proved to exhibit a good effect on patients with HR + /HER2breast cancer in a number of clinical trials, but the problem of drug resistance is inevitable. At present, three specific cdK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have been approved by the USA Food and Drug Administration for the first-line treatment of HR + /HER2breast cancer. The drug resistance mechanisms of cdK4/6 inhibitors can be divided into cell cycle-specific resistance and cell cycle non-specific resistance. With the discovery of the drug resistance mechanism of cdK4/6 inhibitors, various targeted strategies have been proposed. The present review mainly discusses the mechanism of cdK4/6 inhibitors, drug resistance mechanisms and treatment strategies after resistance.

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