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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Cancer biology: mechanism of antitumour action of vorinostat (suberoylanilide hydroxamic acid), a novel histone deacetylase inhibitor.

Histone deacetylase ( HDAC) inhibitors represent a potential new class of antitumor agents. Vorinostat (suberoylanilide hydroxamic acid or SAHA) is a potent inhibitor of HDAC activity and has undergone initial evaluation in several Phase I and II clinical trials. HDACs are enzymes that catalyse the removal of the acetyl moiety from the lysine residues of proteins, including the core nucleosomal histones. Together with histone acetyltransferases (HATs), HDACs regulate the level of protein acetylation. Alterations in both HAT and HDAC activity have been reported to occur in cancer. HAT activity has been found to be disrupted by translocation, amplification, overexpression or mutation in a variety of cancers, including those of haematological or epithelial origin. HDACs have been found to be overexpressed or associated with oncogenic transcription factors. Vorinostat induces growth arrest, differentiation or apoptosis in a variety of transformed cells. The antiproliferative effects of vorinostat are believed to be due to drug-induced accumulation of acetylated proteins, including the core nucleosomal histones and other proteins (e.g., BCL6, p53 and Hsp90). Phase I and II trials have been conducted for the oral formulations of vorinostat, and results show that vorinostat inhibits its target enzyme ( HDAC) in peripheral mononuclear cells and tumour tissue at doses that are well tolerated. Antitumour activity has been seen in patients with both haematological and solid tumours.British Journal of Cancer (2006) 95, S2-S6. doi:10.1038/sj.bjc.6603463 www.bjcancer.com.[1]

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