Histone deacetylase inhibitor induced modulation of anti-estrogen therapy

Cancer Lett. 2009 Aug 8;280(2):184-91. doi: 10.1016/j.canlet.2008.12.026. Epub 2009 Jan 30.

Abstract

Histone deacetylase (HDAC) inhibitors are a novel class of anti-tumor agents with a potential role in the treatment of breast cancer. In ER-positive cells, treatment with selective and non-selective HDAC inhibitors has been associated with a transcriptional down-regulation (and possibly protein modification via the HSP90 chaperone function) of ER and its response genes. In ER-negative cell lines, HDAC inhibitors have been shown to re-establish ER expression. In addition, HDAC inhibitors have been reported to modulate the progesterone receptor. Despite the opposing effects in ER-positive and ER-negative breast cancer cells, the addition of an HDAC inhibitor potentiated and restored the efficacy of anti-estrogen therapy in preclinical models. This has led to the initiation of several clinical trials combining HDAC inhibitors with anti-estrogen therapy. In this review, we will summarize the relationship between estrogen signaling and HDACs, examine how HDAC inhibitors impact this relationship and synergize with anti-estrogens to inhibit tumor growth, and discuss the clinical possibilities and potential of this new approach.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Clinical Trials as Topic
  • Drug Synergism
  • Estrogen Antagonists / administration & dosage
  • Estrogen Antagonists / therapeutic use*
  • Female
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Humans
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / metabolism
  • Receptors, Estrogen / antagonists & inhibitors*
  • Receptors, Estrogen / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogen Antagonists
  • Histone Deacetylase Inhibitors
  • Receptors, Estrogen
  • Histone Deacetylases