title: Mechanisms and clinical significance of histone deacetylase inhibitors: epigenetic glioblastoma therapy.
abstract: Glioblastoma is the most common and deadliest of malignant primary brain tumors (Grade IV astrocytoma) in adults. Current standard treatments have been improving but patient prognosis still remains unacceptably devastating. Glioblastoma recurrence is linked to epigenetic mechanisms and cellular pathways. Thus, greater knowledge of the cellular, genetic and epigenetic origin of glioblastoma is the key for advancing glioblastoma treatment. One rapidly growing field of treatment, epigenetic modifiers; histone deacetylase inhibitors (HDACis), has now shown much promise for improving patient outcomes through regulation of the acetylation states of histone proteins (a form of epigenetic modulation) and other non-histone protein targets. HDAC inhibitors have been shown, in a pre-clinical setting, to be effective anticancer agents via multiple mechanisms, by up-regulating expression of tumor suppressor genes, inhibiting oncogenes, inhibiting tumor angiogenesis and up-regulating the immune system. There are many HDAC inhibitors that are currently in pre-clinical and clinical stages of investigation for various types of cancers. This review will explain the theory of epigenetic cancer therapy, identify HDAC inhibitors that are being investigated for glioblastoma therapy, explain the mechanisms of therapeutic effects as demonstrated by pre-clinical and clinical studies and describe the current status of development of these drugs as they pertain to glioblastoma therapy.
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A.
authors: Philip
authors: P
authors: Lee
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A.
authors: Ben
authors: B
authors: Murphy
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A.
authors: Rickey
authors: R
authors: Miller
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A.
authors: Vivek
authors: V
authors: Menon
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A. Ralph H. Johnson VA Medical Center, Charleston, SC, U.S.A.
authors: Naren L
authors: NL
authors: Banik
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A. Department of Neurological Surgery Ohio State University Wexner Medical College, Columbus, OH, U.S.A.
authors: Pierre
authors: P
authors: Giglio
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A.
authors: Scott M
authors: SM
authors: Lindhorst
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A.
authors: Abhay K
authors: AK
authors: Varma
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A.
authors: William A
authors: WA
authors: Vandergrift
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A.
authors: Sunil J
authors: SJ
authors: Patel
authors: Department of Neurology and Neurosurgery & MUSC Brain & Spine Tumor Program Medical University of South Carolina, Charleston, SC, U.S.A. dasa@musc.edu.
authors: Arabinda
authors: A
authors: Das
mesh_terms: D001549:Benzamides / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D005227:Fatty Acids / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use
chemical_list: D001549:Benzamides; D005227:Fatty Acids; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009842:Oligopeptides
keywords: Clinical trials; epigenetics; glioblastoma; histone deacetylase inhibitor; preclinical trials; review