title: Histone deacetylase inhibitors: a new wave of molecular targeted anticancer agents.
abstract: Epigenetics as well as post-translational modifications of proteins are emerging as novel attractive targets for anti-cancer therapy. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are two classes of enzymes regulating histone acetylation and whose altered activity has been identified in several cancers. In particular, imbalance in histone 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 histone protein substrates such as transcription factors, chaperone proteins or tubulin, undergo acetylation as key post-translation modification regulating their half-life and function. On 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 histone acetylation and molecular basis for their tumor selectivity remains unknown, presenting a challenge for the cancer research community.
authors.affiliation: Experimental Pharmacology Unit, Department of Experimental Oncology, National Cancer Institute Fondazione G. Pascale, Naples, Italy. budillon@fondazionepascale.it
authors.forename: Alfredo
authors.initials: A
authors.lastname: Budillon
authors.forename: Elena
authors.initials: E
authors.lastname: Di Gennaro
authors.forename: Francesca
authors.initials: F
authors.lastname: Bruzzese
authors.forename: Monia
authors.initials: M
authors.lastname: Rocco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Manzo
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010330:Patents as Topic
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases