Histone deacetylase inhibitors – molecular mechanisms of actions and clinical applications

Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression implicated in cancer pathogenesis. Inhibitors of HDACs (HDI) are under investigation as novel anti-cancer drugs, which induce histone hyperacetylation. These agents modulate chromatin structure leadin...

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Bibliographic Details
Main Authors: Aneta Grabarska, Magdalena Dmoszyńska-Graniczka, Ewa Nowosadzka, Andrzej Stepulak
Format: Article
Language:English
Published: Index Copernicus International S.A. 2013-08-01
Series:Postępy Higieny i Medycyny Doświadczalnej
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Online Access:http://journals.indexcopernicus.com/fulltxt.php?ICID=1061381
Description
Summary:Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression implicated in cancer pathogenesis. Inhibitors of HDACs (HDI) are under investigation as novel anti-cancer drugs, which induce histone hyperacetylation. These agents modulate chromatin structure leading to transcriptional changes of a very large number of genes, which affect signaling pathways, inhibit cell cycle progression and angiogenesis, and induce apoptosis in cancer cells. Currently, several HDI are in clinical trials used in monotherapy or in combination with other cytostatics, showing promising anticancer effects. To date, more than 15 HDIs have been found as potential drugs. This paper reviews the molecular mechanisms of HDI action on cancer cells and summarizes clinical trials of the most promising HDIs in the treatment of patients with hematologic malignancies and solid tumors.
ISSN:0032-5449
1732-2693