Related Experiment Video

Updated: Jul 26, 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 the Metastatic Setting: Where Are We Headed?

Elizabeth Sakach1, Merve Keskinkilic2, Sarah Wood3

  • 1Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA. esakach@emory.edu.

Current Treatment Options in Oncology
|June 14, 2023
PubMed
Abstract

Insights

Hormone receptor-positive, HER2-negative metastatic breast cancer treatments have advanced significantly with CDK4/6 inhibitors. Research now focuses on optimal strategies following progression on these therapies for improved patient outcomes.

Area of Science:

  • Oncology
  • Medical Treatments

Background:

  • Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) is the most prevalent subtype.
  • Significant prognostic improvements in metastatic breast cancer are attributed to molecularly targeted therapies.
  • Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment landscape for HR+/HER2- MBC.

Purpose of the Study:

  • To review the current treatment paradigm for HR+/HER2- MBC.
  • To discuss evolving therapeutic strategies following progression on CDK4/6 inhibitors.
  • To explore novel combination therapies and treatment sequencing after CDK4/6i failure.

Main Methods:

  • Literature review of recent clinical trials and expert opinions.
  • Analysis of treatment outcomes and survival data for HR+/HER2- MBC patients.
  • Discussion of emerging therapeutic targets and personalized medicine approaches.

Main Results:

  • CDK4/6 inhibitors have demonstrated substantial improvements in overall survival and quality of life.
  • CDK4/6 inhibitors delay the need for chemotherapy initiation in HR+/HER2- MBC.
  • Optimal treatment sequencing after CDK4/6i progression remains an active area of investigation.

Conclusions:

  • The management of HR+/HER2- MBC is shifting towards personalized, multifaceted treatment strategies.
  • Future research should focus on novel combinations and sequential therapies to overcome resistance to CDK4/6 inhibitors.
  • Continued advancements in targeted therapies promise further improvements in outcomes for patients with metastatic breast cancer.
Keywords:
CDK4/6 inhibitorEndocrine resistance, ctDNAHormone therapyMetastatic breast cancer

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