Related Experiment Video

Updated: Jun 27, 2025

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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CDK4/6 inhibitors: The Devil is in the Detail

Tara Magge1, Sneha Rajendran1, Adam M Brufsky1

  • 1Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.

Current Oncology Reports
|May 7, 2024
PubMed
Abstract

Insights

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are standard for HR+/HER2- breast cancer. While effective, toxicities and cost limit use, and optimal timing requires further research.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Medicine

Background:

  • Hormone receptor (HR)-positive, human epidermal growth factor receptor (HER)2-negative breast cancer is a major subtype.
  • Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized treatment paradigms.

Purpose of the Study:

  • To review the latest clinical evidence on CDK4/6 inhibitors in HR+/HER2- breast cancer.
  • To summarize the efficacy and limitations of CDK4/6 inhibitors in both metastatic and early-stage disease.

Main Methods:

  • Systematic review of recent clinical trials and real-world data.
  • Analysis of progression-free survival and overall survival data.
  • Evaluation of safety profiles and cost-effectiveness.

Main Results:

  • CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) combined with endocrine therapy (ET) improve progression-free survival in metastatic breast cancer (mBC).
  • Ribociclib demonstrates an overall survival benefit in first-line mBC.
  • Abemaciclib is approved for early breast cancer (eBC), with ribociclib showing promising early data for eBC.

Conclusions:

  • CDK4/6 inhibitors are integral to treating HR+/HER2- breast cancer, both metastatic and high-risk early stages.
  • Toxicity, financial burden, and optimal treatment sequencing remain key challenges.
  • Further research is needed to refine the use of CDK4/6 inhibitors and address knowledge gaps.
Keywords:
CDK4/6 inhibitorsEndocrine resistanceEndocrine therapyHormone receptor positive breast cancerTargeted therapies

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