Isocitrate dehydrogenase mutation as a therapeutic target in gliomas

Show simple item record Yozu, Hye-Won en Batchelor, T en 2018-10-16T22:13:56Z en 2017-06 en
dc.identifier.citation Chinese Clinical Oncology 6(3):11 pages Article number 33 Jun 2017 en
dc.identifier.issn 2304-3865 en
dc.identifier.uri en
dc.description.abstract Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG), producing NADPH in the process. More than 80% of low-grade gliomas and secondary glioblastoma (GBM) harbor an IDH mutation. IDH mutations involve the catalytic pocket of the enzyme and lead to a neomorphic ability to produce 2-hydroxyglutarate (2HG) while oxidizing NADPH to NADP+. 2HG is considered as an ‘oncometabolite’ which is thought to be responsible for many, if not all, biologic effects of IDH mutations. 2HG accumulation competitively inhibits α-KG-dependent dioxygenases, including histone lysine demethylases and DNA demethylases, resulting in a hypermethylation phenotype with alterations in cellular epigenetic status as well as a block in cellular differentiation. IDH mutations have been suggested as an important early event in tumorigenesis, however it remains unclear whether IDH mutation by itself causes cancer or if it requires other oncogenic events to initiate tumorigenesis. Significant efforts have been made to better understand the mechanisms of IDH mutations in tumor initiation and progression, and to develop targeted therapies for IDH-mutated tumors. This review provides an overview of the function of mutant IDH, and the current understanding of the role IDH mutations play in gliomagenesis. In addition, several potential therapeutic strategies for IDH-mutant gliomas, including mutant IDH inhibitors which have entered clinical evaluation in glioma patients, will be discussed. en
dc.publisher AME Publishing Company en
dc.relation.ispartofseries Chinese Clinical Oncology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.rights.uri en
dc.title Isocitrate dehydrogenase mutation as a therapeutic target in gliomas en
dc.type Journal Article en
dc.identifier.doi 10.21037/cco.2017.06.11 en
pubs.issue 3 en
pubs.volume 6 en
dc.rights.holder Copyright: AME Publishing Company en en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 668335 en Medical and Health Sciences en Medical Sciences en Pharmacology en
dc.identifier.eissn 2304-3873 en
pubs.number 33 en
pubs.record-created-at-source-date 2017-09-16 en

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