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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Advances in mechanisms of resistance to aromatase inhibitors

Saranya Chumsri1, Amanda Schech, Chakkapong Chakkabat

  • 1Department of Medicine, University of Maryland, School of Medicine and the Greenebaum Cancer Center, Baltimore, MD, USA.

Expert Review of Anticancer Therapy
|February 25, 2014
PubMed

Insights

Understanding aromatase inhibitor (AI) resistance is key for effective breast cancer treatment. Strategies must address acquired resistance via growth factor pathways and innate resistance with combination therapies like fulvestrant and AI.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Aromatase inhibitors (AIs) are crucial in hormone-sensitive breast cancer.
  • Two types of AI resistance exist: acquired and innate, with distinct mechanisms.
  • Interchangeable treatment strategies may be ineffective due to differing resistance pathways.

Purpose of the Study:

  • To differentiate mechanisms of acquired and innate aromatase inhibitor resistance.
  • To explore targeted therapeutic strategies for overcoming AI resistance.
  • To review current and emerging treatment options for AI-resistant breast cancer.

Main Methods:

  • Review of clinical data and research on AI resistance mechanisms.
  • Analysis of targeted therapies for growth factor receptor pathways in acquired resistance.
  • Evaluation of combination therapies for innate resistance, including novel agents.

Main Results:

  • Acquired AI resistance is characterized by growth factor receptor pathway activation.
  • Everolimus plus exemestane is a new standard for acquired resistance.
  • HDAC inhibitors show promise for acquired resistance.
  • Fulvestrant plus AI combination is a new option for innate resistance, especially in de novo metastatic disease.

Conclusions:

  • Tailoring treatment strategies to specific AI resistance types (acquired vs. innate) is essential.
  • Targeting growth factor pathways and utilizing combination therapies represent key advances.
  • Ongoing trials, such as with CDK 4/6 inhibitors, may offer further treatment options.

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