title: Mechanisms of resistance to histone deacetylase inhibitors.
abstract: Histone deacetylase (HDAC) inhibitors are a new class of anticancer agents. HDAC inhibitors induce acetylation of histones and nonhistone proteins which are involved in regulation of gene expression and in various cellular pathways including cell growth arrest, differentiation, DNA damage and repair, redox signaling, and apoptosis (Marks, 2010). The U.S. Food and Drug Administration has approved two HDAC inhibitors, vorinostat and romidepsin, for the treatment of cutaneous T-cell lymphoma (Duvic & Vu, 2007; Grant et al., 2010; Marks & Breslow, 2007). Over 20 chemically different HDAC inhibitors are in clinical trials for hematological malignancies and solid tumors. This review considers the mechanisms of resistance to HDAC inhibitors that have been identified which account for the selective effects of these agents in inducing cancer but not normal cell death. These mechanisms, such as functioning Chk1, high levels of thioredoxin, or the prosurvival BCL-2, may also contribute to resistance of cancer cells to HDAC inhibitors.
authors.affiliation: Department of Cell Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Megan L
authors.initials: ML
authors.lastname: Choy
authors.forename: Paul A
authors.initials: PA
authors.lastname: Marks
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D056572:Histone Deacetylase Inhibitors; D009363:Neoplasm Proteins; D006655:Histone Deacetylases