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Updated: Jul 21, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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CDK4/6 Inhibitor Resistance in Hormone Receptor-Positive Metastatic Breast Cancer: Translational Research, Clinical

Jin Sun Lee1, Hannah Hackbart1, Xiaojiang Cui2

  • 1Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

International Journal of Molecular Sciences
|July 29, 2023
PubMed

Insights

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors improve survival in hormone receptor-positive breast cancer. Understanding resistance mechanisms is key to developing new treatments and improving patient outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib, ribociclib, abemaciclib) have transformed hormone receptor-positive (HR+) breast cancer treatment.
  • These drugs significantly improve progression-free and overall survival, marking a major advancement in care.

Purpose of the Study:

  • To review and outline the mechanisms of resistance to CDK4/6 inhibitors in HR+ breast cancer.
  • To synthesize insights from clinical data and translational research to guide future therapeutic strategies.

Main Methods:

  • Comprehensive review of published clinical data on CDK4/6 inhibitor resistance.
  • Analysis of translational research, including preclinical models and biomarker studies, to elucidate resistance mechanisms.

Main Results:

  • CDK4/6 inhibitors offer substantial clinical benefits but acquired resistance limits long-term efficacy.
  • Multiple complex mechanisms contribute to resistance, necessitating a deeper understanding.

Conclusions:

  • Understanding CDK4/6 inhibitor resistance is critical for developing effective therapeutic strategies.
  • Translational research and clinical insights are vital for overcoming resistance and improving outcomes in metastatic HR+ breast cancer.
Keywords:
CDK4/6 inhibitorsbreast cancerestrogen receptortherapeutic resistance

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