Histone deacetylase inhibitors: A new wave of molecular targeted anticancer agents

Epigenetics as well as post-translational modifications of proteins are emerging as novel attractive targets far anti-cancer therapy. Histone acetyltransferases (HATs) and historic deacetylases (HDACs) are two classes of enzymes regulating historic acetylation and whose altered activity has been identified in several cancers. In particular, imbalance in historic acetylation can lead to changes in chromatin structure and transcriptional dysregulation of genes that are involved in the control of proliferation, cell-cycle progression, differentiation and/or apoptosis. In addition, several non historic protein substrates such as transcription factors, chaperone proteins or tubulin, undergo acetylation as key post-translation modification regulating their half-life and function. Oil this regard, several inhibitors of HDAC, selected by academic as well as industrial research, have been recently shown to induce growth arrest and apoptosis in a variety of human cancer cells and have been patented as anti-cancer agents. Although several clinical studies with HDAC inhibitors are ongoing, their mechanism of action cannot be solely attributed to the level of historic acetylation and molecular basis for their tumor selectivity remains unknown, presenting a challenge for the cancer research community.