CDK4/6 inhibitor resistance mechanisms and treatment strategies (Review)
Jinyao Huang, Liang Zheng, Zicheng Sun, Jie Li
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)<sup>+</sup>/human epidermal growth factor receptor 2 (HER2)<sup>‑</sup> 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<sup>+</sup>/HER2<sup>‑</sup> 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<sup>+</sup>/HER2<sup>‑</sup> 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.