Journal
MEDICINAL RESEARCH REVIEWS
Volume 25, Issue 3, Pages 261-309Publisher
WILEY
DOI: 10.1002/med.20024
Keywords
epigenetics; HDAC inhibitors; clinical trials; anticancer chemotherapy; class selectivity
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The reversible hi stone acetylation and deacetylation are epigenetic phenomena that play critical roles in the modulation of chromatin topology and the regulation of gene expression. Aberrant transcription due to altered expression or mutation of genes that encode histone acetyltransferase (HAT) or histone deacetylase (HDAC) enzymes or their binding partners, has been clearly linked to carcinogenesis. The histone deacetylase inhibitors are a new promising class of anticancer agents (some of which in clinical trials), that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell-cycle arrest, terminal differentiation, and/or apoptosis. This report reviews the chemistry and the biology of HDACs and HDAC inhibitors, laying particular emphasis on agents actually in clinical trials for cancer therapy and on new potential anticancer lead compounds more selective and less toxic. (c) 2005 Wiley Periodicals, Inc.
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