International Journal of Medical Sciences

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17 October 2017

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Int J Med Sci 2015; 12(3):201-213. doi:10.7150/ijms.11047

Review

New Developments in the Pathogenesis and Therapeutic Targeting of the IDH1 Mutation in Glioma

Lilia Dimitrov1,2*, Christopher S. Hong2*, Chunzhang Yang2, Zhengping Zhuang2✉, John D. Heiss2✉

1. Barts and the London School of Medicine and Dentistry, Greater London, E1 2AD, United Kingdom
2. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
* Equal contribution

Abstract

In the last five years, IDH1 mutations in human malignancies have significantly shaped the diagnosis and management of cancer patients. Ongoing intense research efforts continue to alter our understanding of the role of the IDH1 mutation in tumor formation. Currently, evidence suggests the IDH1 mutation to be an early event in tumorigenesis with multiple downstream oncogenic consequences including maintenance of a hypermethylator phenotype, alterations in HIF signalling, and disruption of collagen maturation contributing to a cancer-promoting extracellular matrix. The most recent reports elucidating these mechanisms is described in this review with an emphasis on the pathogenesis of the IDH1 mutation in glioma. Conflicting findings from various studies are discussed, in order to highlight areas warranting further research. Finally, the latest progress in developing novel therapies against the IDH1 mutation is presented, including recent findings from ongoing phase 1 clinical trials and the exciting prospect of vaccine immunotherapy targeting the IDH1 mutant protein.

Keywords: IDH1 protein, glioma, DNA methylation, HIF1A protein, molecular targeted therapy, review

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Dimitrov L, Hong CS, Yang C, Zhuang Z, Heiss JD. New Developments in the Pathogenesis and Therapeutic Targeting of the IDH1 Mutation in Glioma. Int J Med Sci 2015; 12(3):201-213. doi:10.7150/ijms.11047. Available from http://www.medsci.org/v12p0201.htm