title: Targeted cancer therapy: giving histone deacetylase inhibitors all they need to succeed.
abstract: Histone deacetylase inhibitors (HDACis) have now emerged as a powerful new class of small-molecule therapeutics acting through the regulation of the acetylation states of histone proteins (a form of epigenetic modulation) and other non-histone protein targets. Over 490 clinical trials have been initiated in the last 10 years, culminating in the approval of two structurally distinct HDACis - SAHA (vorinostat, Zolinza™) and FK228 (romidepsin, Istodax™). However, the current HDACis have serious limitations, including ineffectively low concentrations in solid tumors and cardiac toxicity, which is hindering their progress in the clinic. Herein, we review the primary paradigms being pursued to overcome these hindrances, including HDAC isoform selectivity, localized administration, and targeting cap groups to achieve selective tissue and cell type distribution.
authors.affiliation: School of Chemistry & Biochemistry, Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
authors.forename: Berkley E
authors.initials: BE
authors.lastname: Gryder
authors.forename: Quaovi H
authors.initials: QH
authors.lastname: Sodji
authors.forename: Adegboyega K
authors.initials: AK
authors.lastname: Oyelere
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D020033:Protein Isoforms; D006655:Histone Deacetylases