Finding the place of histone deacetylase inhibitors in prostate cancer therapy

Deborah L. Marrocco-Tallarigo, Margaret M. Centenera, Howard I. Scher, Wayne D. Tilley, Lisa M. Butler

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Histone deacetylase inhibitors (HDACIs) are showing promise as therapeutic agents for hematological malignancies and solid tumors. In the case of prostate cancer, HDACIs are effective at inhibiting proliferation and inducing apoptosis in a range of in vitro and in vivo experimental models. Recent studies have revealed that the actions of HDACIs in prostate cancer cells extend beyond regulation of histone acetylation and affect proteins involved in maintaining cellular homeostasis and tumor progression, including the androgen receptor, p21WAF1 and VEGF. The broad spectrum of HDACI targets has allowed rational design of combinations with other therapeutic agents to target multiple pathways involved in prostate cancer progression, including angiogenesis and androgen signaling. In particular, synergistic inhibition of prostate cancer cell growth has been demonstrated using HDACIs in combination with radio- and chemo-therapy, Apo2L/TRAIL, angiogenesis inhibitors, heat-shock protein 90 inhibitors and androgen receptor antagonists. This review examines the current understanding of the actions of HDACIs in prostate cancer cells, both in a laboratory and a clinical context and discusses the potential utility of combination strategies for the treatment of prostate cancer.

LanguageEnglish
Pages619-630
Number of pages12
JournalExpert Review of Clinical Pharmacology
Volume2
Issue number6
DOIs
Publication statusPublished - 1 Dec 2009

Keywords

  • Androgen signaling
  • Clinical trials
  • Combination therapies
  • Histone deacetylase inhibitors
  • Prostate cancer

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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