title: Pharmacogenomics and histone deacetylase inhibitors.
abstract: The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment. This review provides an overview of clinical studies on the effects of polymorphisms on the pharmacokinetics, efficacy or toxicities of HDIs including belinostat, romidepsin, vorinostat, panobinostat, VPA and a number of novel compounds currently being tested in Phase I and II trials. Although pharmacogenomic studies for HDIs are scarce, available data indicate that therapy with belinostat (UGT1A1), romidepsin (ABCB1), vorinostat (UGT2B17) or VPA (UGT1A6) could be optimized by upfront genotyping.
authors: Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Andrew Kl
authors: AK
authors: Goey
authors: Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Tristan M
authors: TM
authors: Sissung
authors: Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Cody J
authors: CJ
authors: Peer
authors: Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: William D
authors: WD
authors: Figg
mesh_terms: D047630:Depsipeptides / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D000077767:Panobinostat; D010597:Pharmacogenetics; D013449:Sulfonamides / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use; D000077337:Vorinostat
chemical_list: D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D013449:Sulfonamides; D000077337:Vorinostat; D014635:Valproic Acid; D000077767:Panobinostat; C087123:romidepsin; C487081:belinostat
keywords: HDAC inhibitors; UGT1A1; belinostat; panobinostat; pharmacogenomics; romidepsin; valproic acid; vorinostat