Authors
Jiayi Wu, Yinglu Lai, Guang Lu
Published in
Breast care (Basel, Switzerland). Apr 29, 2026. Epub Apr 29, 2026.
Abstract
The efficacy of CDK4/6 inhibitors in hormone receptor-positive breast cancer has catalyzed the exploration of other cyclin-dependent kinases (CDKs) as therapeutic targets. Numerous CDK family members are aberrantly activated in breast cancer, driving disease progression via both cell cycle-dependent and independent mechanisms, while unmet clinical needs persist in overcoming therapy resistance and treating aggressive subtypes.
This review synthesizes current knowledge on the pathological roles of key CDKs (CDK 1, 2, 5, 7, 8, 9, 12) in breast cancer, emphasizing their functions in promoting proliferation, metastasis, and resistance to chemotherapy, anti-HER2 agents, and CDK4/6 inhibitors. We provide a systematic update on the development and clinical trial progress of novel CDK inhibitors targeting these resistance mechanisms and examine innovative applications including combinations with immunotherapies and rational design of CDK inhibitor-based antibody-drug conjugates.
Targeting a broader spectrum of CDKs represents a viable and promising strategy to address unmet clinical needs in breast cancer. The expanding landscape of CDK-targeted therapies - both as single agents and rational combinations - is poised to significantly reshape future treatment paradigms, particularly for overcoming therapy resistance and managing aggressive subtypes.
PMID:
42404635
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.
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