Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer

Br J Cancer. 2024 May;130(8):1239-1248. doi: 10.1038/s41416-024-02589-8. Epub 2024 Feb 14.

Abstract

Background: Cyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies.

Methods: In this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer.

Results: Significant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging.

Conclusion: CDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinases / metabolism
  • Cyclin-Dependent Kinases / therapeutic use
  • Female
  • Humans
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / genetics

Substances

  • Cyclin-Dependent Kinases
  • Protein Kinase Inhibitors
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6