期刊
BREAST CANCER RESEARCH
卷 24, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13058-022-01510-6
关键词
Cyclin-dependent kinase; CDK4; 6; Cell cycle; Breast cancer; Combination therapy; Drug resistance
类别
资金
- National Health and Medical Research Council of Australia [GNT1177357]
- US National institutes of Health [P50 CA168504]
- University of Melbourne
Pharmacological inhibitors of CDK4/6 are standard therapies for hormone receptor-positive breast cancer, primarily by suppressing tumor cell proliferation. Recent data suggests that these inhibitors also have other effects in tumor and stromal compartments, which may explain their clinical activity.
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.
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