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Epigenetic modulation: a novel therapeutic target for overcoming hormonal therapy resistance

Paromita Raha1, Scott Thomas, Pamela N Munster

  • 1Department of Medicine, Hematology/Oncology Division. Room A722, University of California, 1600 Divisadero St, San Francisco, CA 94115-1770, USA.

Epigenomics
|December 1, 2011
PubMed

Insights

Antiestrogen therapy for breast cancer faces resistance. Epigenetic regulation of gene expression is a key factor in both de novo and acquired resistance, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Antiestrogen therapy is a cornerstone in breast cancer treatment, targeting estrogen receptor activity.
  • Therapeutic resistance, both de novo and acquired, significantly limits the efficacy of antiestrogen treatments.
  • Understanding resistance mechanisms is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To review the current understanding of antiestrogen resistance mechanisms in breast cancer.
  • To highlight the role of epigenetic regulation in the development of resistance.
  • To examine therapeutic approaches targeting epigenetic machinery to overcome resistance.

Main Methods:

  • Literature review focusing on epigenetic mechanisms in antiestrogen resistance.
  • Analysis of studies investigating epigenetic modifications and their impact on gene expression in resistant breast cancer models.
  • Examination of preclinical and clinical studies evaluating epigenetic therapies.

Main Results:

  • Epigenetic dysregulation, including DNA methylation and histone modifications, significantly contributes to both de novo and acquired antiestrogen resistance.
  • Altered gene expression patterns driven by epigenetic changes are implicated in promoting tumor growth and survival despite antiestrogen treatment.
  • Targeting epigenetic modifiers has shown promise in preclinical models for restoring sensitivity to antiestrogens.

Conclusions:

  • Epigenetic regulation plays a pivotal role in the development of antiestrogen resistance in breast cancer.
  • Targeting epigenetic machinery represents a promising strategy to overcome resistance and improve treatment outcomes.
  • Further research and clinical trials are warranted to fully exploit epigenetic therapies in breast cancer management.

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