title: Epigenetic drugs against cancer: an evolving landscape.
abstract: Alteration of the chromatin orchestra seems to play a critical role in cancer. In recent years, in-depth studies of epigenetic machinery and its deregulation have led to the development and use of a wide range of modulatory molecules directed not only at chromatin enzymes (histone acetyltransferases, histone deacetylases, histone methyltransferases, histone demethylases and DNA methyltransferases) but also toward the emerging class of chromatin-associated proteins, so-called "histone readers." Chromatin modifiers are attractive therapeutic targets for the development of new cancer therapies. Many are currently approved by the US Food and Drug Administration and used to treat different malignancies. Specifically, inhibitors of DNA methyltransferases, such as azacitidine and decitabine, have been approved for the treatment of myelodysplastic syndrome, while inhibitors of histone deacetylases, including vorinostat and romidepsin, have been approved for cutaneous T-cell lymphoma. The bromodomain and extra-terminal inhibitors JQ1, IBET762 and IBET151 have performed extremely well in preclinical settings, suggesting that they may be promising molecules for the treatment of some type of tumors. This review focuses on epidrugs and their possible application, with particular emphasis on their mechanism of action as well as their present status in clinical and preclinical trials.
authors.affiliation: Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Costanzo
authors.forename: Nunzio
authors.initials: N
authors.lastname: Del Gaudio
authors.forename: Antimo
authors.initials: A
authors.lastname: Migliaccio
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D035843:Biomedical Research / Q000639:trends; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D015195:Drug Design; D055808:Drug Discovery / Q000639:trends; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D009363:Neoplasm Proteins