Singlet Anticancer Therapy Through Epi-Weapons Histone Deacetylase Inhibitors and Its Shortcomings

Abstract

Appalling toxicities and chemoresistance associated with conventional anticancer therapies raise applicability related concerns (Howard et al. 2016). This emphasizes the dire need of novel therapies which are well tolerated and concurrently effective (Ganai et al. 2017; Guimaraes et al. 2013). Experimental evidences certify the implications of epigenetic mechanisms in tumour onset, progression and drug resistance (Hrabeta et al. 2014; Wilting and Dannenberg 2012). Histone deacetylases (HDACs), the metalloenzymes altering the chromatin topology through deacetylation of nucleosomal histones epigenetically silence genes involved in inhibition of tumour development (Ma et al. 2015). Anomalous expression of HDACs through alteration of cellular acetylation homeostasis causes transcriptional deregulation thereby making the conditions convenient for genesis and advancement of cancer (Li and Seto 2016; Saha and Pahan 2006). Thus fine tuning the gene expression by restoration of acetylation homeostasis through intervention of these HDACs has emerged as a promising strategy in epigenetic-based anticancer therapy. These small molecules, by name histone deacetylase inhibitors (HDACi), block the enzymatic function of HDACs through binding at their active site (Lakshmaiah et al. 2014; Lombardi et al. 2011).