Abstract
Histone acetylation and histone deacetylation play key roles in the epigenetic regulation. Thus, inhibition of deacetylation controlled by histone deacetylases may result in chromatin remodeling, upregulation of key tumor repressor genes, differentiation or apoptosis. Therefore many naturally occurring and synthetic histone deacetylase inhibitors have been shown to display potent anticancer activities in preclinical studies. The exact mechanism by which histone deacetylases exert their effect, however, is still obscure; in any case it is more complicated than originally understood. Although several representatives of this novel class of therapeutic agents are currently at early stages of clinical development, rational design leading to highly selective histone deacetylase inhibitors against histone deacetylase isoforms will not only probably offer more potent anticancer drugs, but also critical insights into their mechanism of action.
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