title: Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer.
abstract: Histone deacetylases (HDACs) regulate the acetylation of a variety of histone and nonhistone proteins, controlling the transcription and regulation of genes involved in cell cycle control, proliferation, survival, DNA repair and differentiation. Unsurprisingly, HDAC expression is frequently altered in hematologic and solid tumor malignancies. Two HDAC inhibitors (vorinostat and romidepsin) have been approved by the US FDA for the treatment of cutaneous T-cell lymphoma. As single agents, treatment with HDAC inhibitors has demonstrated limited clinical benefit for patients with solid tumors, prompting the investigation of novel treatment combinations with other cancer therapeutics. In this article, the rationales and clinical progress of several combinations with HDAC inhibitors are presented, including DNA-damaging chemotherapeutic agents, radiotherapy, hormonal therapies, DNA methyltransferase inhibitors and various small-molecule inhibitors. The future application of HDAC inhibitors as a treatment for cancer is discussed, examining current hurdles to overcome before realizing the potential of this new approach.
authors.affiliation: Department of Medicine, Hematology/Oncology Division. University of California-San Francisco, 1600 Divisadero Street, San Francisco, CA 94115, USA.
authors.forename: K Ted
authors.initials: KT
authors.lastname: Thurn
authors.forename: Scott
authors.initials: S
authors.lastname: Thomas
authors.forename: Amy
authors.initials: A
authors.lastname: Moore
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Munster
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002843:Chromatin / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases