생화학분자생물학회

	Hee Won Yang ( hy2602@columbia.edu )
	01/2019 - present	Assistant Professor, Department of Pathology and Cell Biology, Columbia University, USA
	01/2019 - present	Member of the Herbert Irving Comprehensive Cancer Center, Columbia University, USA
	11/2024 - present	Member of Edward P. Evans Center for Myelodysplastic Syndromes, Columbia University, USA
	12/2012 - 12/2018	Postdoctoral Fellow, Stanford University, USA
	02/2012 - 12/2012	Postdoctoral Fellow, KAIST, Korea
	03/2008 - 02/2012	PhD, KAIST, Korea

Targeting CDK4/6 in breast cancer

Dysregulation of the cell cycle machinery, particularly overactivation of cyclin-dependent kinases 4 and 6 (CDK4/6), is a hallmark of breast cancer pathogenesis. The introduction of CDK4/6 inhibitors has transformed the treatment landscape for hormone receptor-positive (HR+) breast cancer by effectively targeting abnormal cell cycle progression. However, despite their initial clinical success, drug resistance remains a significant challenge, with no reliable biomarkers available to predict treatment response or guide strategies for managing resistant populations. Consequently, numerous studies have sought to investigate the mechanisms driving resistance to optimize the therapeutic use of CDK4/6 inhibitors and improve patient outcomes. This review examines the molecular mechanisms regulating the cell cycle, current clinical applications of CDK4/6 inhibitors in breast cancer, and key mechanisms contributing to drug resistance. Additionally, we discuss emerging predictive biomarkers and highlight potential directions for overcoming resistance and enhancing therapeutic efficacy.

Exp Mol Med. 2025 Feb;57(2):312-322. doi: 10.1038/s12276-025-01395-3.
https://pubmed.ncbi.nlm.nih.gov/39930131/