Role of HDACs and DNMTs in cancer therapy: A review

Author(s): Yogesh Kumar Walia* and Vishal Sharma**

Although cancer has been considered as untreatable till now, but development of several biological agents have improved the survival and quality of life in some patients. A class of agents targeting epigenetic modifier enzymes have emerged with huge potential in cancer therapy.Novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity and DNMT inhibitory activity are attractive therapeutic approach in recent time. Clinically, it is much simple to inhibit an enzyme than to induce one and this has directed the recent research to a new class of enzymes i.e. DNMT and HDAC. As a result of the earlier work it has become clear that HDACs are unique player inchromatin architecture, thus affect protein expression by altering the accessibility of Dna to the transcriptional machinery, which in turn affect transcriptional control and also activation of many tumour suppressor genes. Instead of it DNMTs areassociated with hypermethylation of promoter and decrease its accessibility for transcriptional machinery. The extensive outcome of research in terms of structure, class, size etc. offers opportunities for the development of HDACi and DNMTi with improved specificity. In recent years, an increasing number of structurally diverse inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells both in-vitroand in-vivo. The question, that how epigenetic modifications associated with DNA or histones increases or decreases the accessibility of DNA to various factors that are involved in the reading of the DNA create interest in the researchers and lead to extensive research in this field.


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