Anticancer activities of histone deacetylase inhibitors

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Abstract
Histone deacetylase inhibitors are novel anticancer agents that induce tumour cell death, differentiation, and/or cell cycle arrest. As well as their intrinsic effects on tumour cells, histone deacetylase inhibitors may additionally affect neoplastic growth and survival by regulating host immune responses and tumour vasculature. The pleiotropic cellular effects of HDACi can act cooperatively to mediate potent anti-tumour activities; however, the molecular processes underlying these effects of HDACi remain to be fully elucidated. The activity of diverse non-histone proteins can be regulated by acetylation indicating that HDACi may have a much broader effect on cellular physiology than originally understood. Altered gene expression through the effects of HDACi on the activity of transcription factors and transcription-independent effects of HDACi are also important in their anticancer activities. In preclinical studies, several classes of HDACi have been found to have potent anticancer activities, and some have demonstrated promising therapeutic potential in early clinical trials for haematological malignancies such as cutaneous T-cell lymphoma, myelodysplastic syndromes and diffuse B-cell lymphoma. While HDACi show promise as single agent anticancer drugs, their use in combination with other agents may prove to be their most useful application. Already, HDACi have been shown to function synergistically with a host of structurally and functionally diverse chemical compounds and biologically active polypeptides.