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Resistance to CDK4/6 Inhibitors in Estrogen Receptor-Positive Breast Cancer

Erin R Scheidemann1, Ayesha N Shajahan-Haq1

  • 1Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA.

International Journal of Molecular Sciences
|November 27, 2021
PubMed

Insights

Estrogen receptor-positive breast cancer treatments like CDK4/6 inhibitors face resistance. Identifying biomarkers for resistant patients can guide alternative therapies, improving outcomes for ER+ breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Estrogen receptor-positive (ER+) breast cancer is the most prevalent subtype.
  • Antiestrogen therapies, while effective, led to treatment resistance.
  • Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors emerged as a successful therapeutic strategy for ER+ breast cancer.

Purpose of the Study:

  • To review the mechanisms of resistance to CDK4/6 inhibitors in ER+ breast cancer.
  • To discuss strategies for overcoming acquired and intrinsic resistance.
  • To highlight the need for predictive biomarkers for CDK4/6 inhibitor therapy.

Main Methods:

  • Literature review of preclinical and clinical studies on CDK4/6 inhibitor resistance.
  • Analysis of identified resistance mechanisms, including signaling pathway activation and genetic alterations.
  • Evaluation of therapeutic strategies targeting these resistance pathways.

Main Results:

  • Resistance to CDK4/6 inhibitors is a significant clinical challenge, arising from diverse mechanisms.
  • Targeting identified resistance pathways has shown promise in preclinical and clinical settings.
  • Overcoming resistance often involves combination therapies or novel therapeutic approaches.

Conclusions:

  • Understanding resistance mechanisms is crucial for optimizing CDK4/6 inhibitor therapy.
  • Development of predictive biomarkers is essential to personalize treatment strategies.
  • Future research should focus on identifying patients likely to resist CDK4/6 inhibitors for alternative treatment selection.
Keywords:
CDK4/6 inhibitorsER+ breast cancerabemaciclibantiestrogenspalbociclibribociclib

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