Related Experiment Video

Updated: Apr 24, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

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Targeting cyclin-dependent kinases in cancer: emerging therapeutics and clinical strategies

Harold N Tan1, Giuseppe Curigliano2, Timothy A Yap3

  • 1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Trends in Cancer
|April 22, 2026
PubMed

Insights

Cyclin-dependent kinase (CDK) inhibitors show promise in cancer therapy, but resistance and toxicity limit their use. New CDK-targeting drugs and strategies are emerging to improve efficacy and safety in precision oncology.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cyclin-dependent kinases (CDKs) are crucial regulators of the cell cycle, and their aberrant activity is implicated in cancer development.
  • Current CDK4/6 inhibitors are effective for hormone receptor-positive, HER2-negative breast cancer but face challenges like adaptive resistance and toxicity.
  • Limited efficacy in other cancer types necessitates the development of novel CDK-targeting agents.

Purpose of the Study:

  • To review recent advancements in CDK-targeted cancer therapies.
  • To discuss emerging strategies and novel modalities for CDK inhibition.
  • To identify challenges and future directions for optimizing CDK-directed therapies in precision oncology.

Main Methods:

  • Literature review of preclinical and clinical studies on CDK inhibitors.
  • Synthesis of data on novel CDK inhibitors, including selective and pan-CDK agents.
  • Analysis of emerging therapeutic modalities like proteolysis-targeting degraders.

Main Results:

  • Development of CDK4-selective, CDK2-selective, and pan-CDK2/4/6 inhibitors to overcome resistance and improve tolerability.
  • Emergence of novel agents such as proteolysis-targeting degraders and molecular glue degraders.
  • Several new CDK-directed candidates are undergoing early-phase clinical trials.

Conclusions:

  • New generations of CDK inhibitors and novel modalities represent a promising frontier in cancer treatment.
  • Addressing challenges in efficacy and safety is crucial for successful clinical integration.
  • Future research should focus on integrating these CDK-directed strategies into personalized cancer treatment plans.
Keywords:
cell cyclecyclin-dependent kinase inhibitorscyclin-dependent kinasesdrug resistanceprecision medicine

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