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

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+/HER2(-) breast 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+/HER2(-) breast 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.

Automated summary

Breast cancer has become a major threat to women's health globally, especially the hormone receptor (HR)(+)/human epidermal growth factor receptor 2 (HER2)(-) luminal subtype breast cancer. The use of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors has shown promising results in clinical trials for HR+/HER2(-) breast cancer patients, but drug resistance remains a challenge. Three specific CDK4/6 inhibitors have been approved for first-line treatment in the United States. This review focuses on the mechanisms of CDK4/6 inhibitors, drug resistance mechanisms, and treatment strategies.