Epigenetic therapy in cancer: molecular background and clinical development of histone deacetylase and DNA methyltransferase inhibitors.

The past decades have brought major breakthroughs in the identification of distinct genetic alterations (eg, mutations, chromosomal aberrations) in various human tumors, leading to the development and clinical use of novel target-specific antibodies and small molecules. Recently, variable modifications of chromatin elements have become the focus of cell biology research. Compounds that inhibit the key chromatin-modifying enzyme classes of histone deacetylase (HDAC) and DNA methyltransferase (DNMT) are currently being evaluated in various preclinical studies and clinical trials. The overexpression of both HDAC and DNMT has been demonstrated to be associated with the epigenetic inactivation of tumor suppressor genes, as well as cell cycle and apoptosis regulators. In addition, inhibitors of HDAC and DNMT possess direct cytotoxic properties, and can sensitize tumor cells to conventional radiotherapy and chemotherapy.