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Histone deacetylases and cancer: causes and therapies

Histone deacetylases and cancer: causes and therapies Histone acetylation is determined by the activities of two classes of enzyme: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Histones are the core protein components of nucleosomes and their acetylation status regulates, in part, gene expression. Deacetylated histones are generally associated with silencing gene expression; so the acetylation of histones is generally associated with derepression of gene expression. Aberrant acetylation is associated with several solid tumours and haematological malignancies. Several types of compound have been identified that inhibit HDACs and cause accumulation of acetylated histones in normal and tumour tissues. They also inhibit transformed cell growth in vitro and in vivo. Inhibition of HDACs with hydroxamic-acid-based hybrid polar compounds — for example, suberoylanilide hydroxamic acid (SAHA) — alters transcription of very few expressed genes. Several HDAC inhibitors are in clinical trials with cancer patients. They are well tolerated, cause accumulation of acetylated histones in peripheral mononuclear cells and tumours and, more importantly, have clinical activity with objective tumour regression. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Cancer Springer Journals

Histone deacetylases and cancer: causes and therapies

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References (93)

Publisher
Springer Journals
Copyright
Copyright © 2001 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Cancer Research
ISSN
1474-175X
eISSN
1474-1768
DOI
10.1038/35106079
Publisher site
See Article on Publisher Site

Abstract

Histone acetylation is determined by the activities of two classes of enzyme: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Histones are the core protein components of nucleosomes and their acetylation status regulates, in part, gene expression. Deacetylated histones are generally associated with silencing gene expression; so the acetylation of histones is generally associated with derepression of gene expression. Aberrant acetylation is associated with several solid tumours and haematological malignancies. Several types of compound have been identified that inhibit HDACs and cause accumulation of acetylated histones in normal and tumour tissues. They also inhibit transformed cell growth in vitro and in vivo. Inhibition of HDACs with hydroxamic-acid-based hybrid polar compounds — for example, suberoylanilide hydroxamic acid (SAHA) — alters transcription of very few expressed genes. Several HDAC inhibitors are in clinical trials with cancer patients. They are well tolerated, cause accumulation of acetylated histones in peripheral mononuclear cells and tumours and, more importantly, have clinical activity with objective tumour regression.

Journal

Nature Reviews Cancer – Springer Journals

Published: Dec 1, 2001

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