Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer
- Journal Title
- Breast Cancer Research
- Publication Type
- Review
- Abstract
- Pharmacological inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) are now an established standard of care for patients with advanced hormone receptor-positive breast cancer. The canonical mechanism underlying CDK4/6 inhibitor activity is the suppression of phosphorylation of the retinoblastoma tumor suppressor protein, which serves to prevent cancer cell proliferation. Recent data suggest that these agents induce other diverse effects within both tumor and stromal compartments, which serve to explain aspects of their clinical activity. Here, we review these phenomena and discuss how they might be leveraged in the development of novel CDK4/6 inhibitor-containing combination treatments. We also briefly review the various known mechanisms of acquired resistance in the clinical setting.
- Keywords
- *Breast Neoplasms/pathology; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Protein Kinase Inhibitors/pharmacology/therapeutic use; Breast cancer; Cdk4/6; Cell cycle; Combination therapy; Cyclin-dependent kinase; Drug resistance
- Department(s)
- Laboratory Research; Medical Oncology
- PubMed ID
- 35248122
- Publisher's Version
- https://doi.org/10.1186/s13058-022-01510-6
- Open Access at Publisher's Site
https://doi.org/10.1186/s13058-022-01510-6- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-05-09 06:08:22
Last Modified: 2025-05-09 06:09:24