Histone Deacetylase Inhibitors and Anticancer Therapy

Recent reports have shown that pharmacological manipulation of chromatin remodeling by histone deacetylase (HDAC) inhibitors, might develop into a potent and specific strategy for the treatment of cancer. Alterations in histone acetylation may lead to changes in chromatin structure and transcriptional dysregulation of genes that are implicated in controlling either cell cycle progression or pathways regulating cell differentiation and/or apoptosis. Dimethyl sulphoxide was one of the first chemicals to be identified as an inducer of transformed cell differentiation. In the class of HDAC inhibitors, now included a short-chain fatty acids, such as 4-phenylbutyrate and valporic acid, hydroxamic acids, such as suberoylanilide hydroxamic acid (SAHA), pyroxamide, trichostatin A, oxamflatin and CHAPSs, cyclic tetrapeptides, such as trapoxin, apicidin and depsipeptide-also known as FK-228 or FR 901228, and benzamides, such as MS-275. First clinical studies have shown that histone hyperacetylation can be achieved safely in humans and that treatment of cancer with such agents seems to become possible. Thus, HDAC inhibitors remains one of the most promising class of new anticancer agents. Further studies are needed in order to delineate the optimal dosage, the duration of therapy and possibly the efficacy of other agents able to synergize with HDAC inhibitors in the fight against cancer.