Int J Med Sci 2015; 12(3):201-213. doi:10.7150/ijms.11047
New Developments in the Pathogenesis and Therapeutic Targeting of the IDH1 Mutation in Glioma
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
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
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