Related Experiment Video

Updated: May 10, 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 inhibition in early and advanced hormone receptor-positive, HER2-negative breast cancer

Sudha Yarlagadda1, Matheus de Oliveira Andrade2, Rita Nanda1,3

  • 1Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.

Expert Review of Anticancer Therapy
|April 26, 2025
PubMed
Abstract

Insights

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are crucial for treating advanced and high-risk early-stage hormone receptor-positive, HER2-negative breast cancer. Ongoing research aims to improve outcomes with novel combinations, though predictive biomarkers are still needed.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a cornerstone therapy for hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer.
  • These inhibitors, including abemaciclib and ribociclib, are also approved for high-risk, early-stage HR+/HER2- breast cancer.

Purpose of the Study:

  • To review the scientific basis for CDK4/6 inhibition in HR+/HER2- breast cancer.
  • To summarize pivotal clinical trials leading to regulatory approvals.
  • To discuss ongoing trials exploring novel combinations for improved patient outcomes.

Main Methods:

  • Comprehensive literature review of PubMed MEDLINE from January 1, 2000, to December 31, 2024.
  • Analysis of clinical trial data and regulatory approvals for CDK4/6 inhibitors.
  • Synthesis of current research on novel therapeutic combinations.

Main Results:

  • CDK4/6 inhibitors are integral to managing both advanced and early-stage HR+/HER2- breast cancer.
  • Predictive biomarkers for CDK4/6 inhibitor benefit are still elusive.
  • Clinical and pathological features are currently key for patient selection in the early-stage setting.

Conclusions:

  • CDK4/6 inhibitors are established treatments for HR+/HER2- breast cancer.
  • Further research is focused on novel combinations to enhance efficacy.
  • Identifying predictive biomarkers remains a critical area for future investigation.
Keywords:
AbemaciclibCDK 4/6 inhibitorhormone receptor-positive breast cancerpalbociclibribociclib

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