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

Int J Mol Med. 2022 Oct;50(4):128. doi: 10.3892/ijmm.2022.5184. Epub 2022 Aug 31.

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)+/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.

Keywords: CDK4/6; breast cancer; drug resistance; mechanisms; strategies.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6*
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Protein Kinase Inhibitors
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6

Grants and funding

This study was supported by the National Natural Science Foundation of China (grant no. 82172917).