Isocitrate Dehydrogenase Mutations in Glioma: From Basic Discovery to Therapeutics Development.

Juan Huang,Jialong Yu,Nanqu Huang,Hang Li,Lin Tu,Yong Luo

doi:10.3389/fonc.2019.00506

Abstract

Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the Krebs cycle that plays an important role in energy metabolism. In recent years, it has been found that IDH mutations are closely related to the occurrence and development of glioma, and it is a notable potential therapeutic target. First, IDH mutations can produce high levels of 2-hydroxyglutaric acid (2-HG), thereby inhibiting glioma stem cell differentiation. At the same time, IDH mutations can upregulate vascular endothelial growth factor (VEGF) to promote the formation of the tumor microenvironment. In addition, IDH mutations can also induce high levels of hypoxia-inducible factor-1α (HIF-1α) to promote glioma invasion. Ultimately, these changes will lead to the development of glioma. Currently, a large number of IDH inhibitors and vaccines have entered clinical trials, representing progress in the treatment of glioma patients.

Highlights

Glioma is the most frequent brain tumor, accounting for more than 60% of primary brain tumors [1]
Oxygen content is closely related to the distribution of microvessels in addition to the migration of glioma cells, and the microvascular proliferation of tumor abnormalities is closely related to the formation of the tumor microenvironment
These results indicate the potential of the vaccine in the treatment of glioma patients with IDH1 mutation

Summary

INTRODUCTION

Glioma is the most frequent brain tumor, accounting for more than 60% of primary brain tumors [1]. IDH catalyses the production of α-KG from isocitrate, and when the IDH1/2 gene is mutated, its corresponding function and product will change This protein inhibits glioma stem cell differentiation by producing high levels of 2-hydroxyglutaric acid (2-HG), upregulates vascular endothelial growth factor (VEGF) to promote tumor microenvironment formation, and produces. Oxygen content is closely related to the distribution of microvessels in addition to the migration of glioma cells, and the microvascular proliferation of tumor abnormalities is closely related to the formation of the tumor microenvironment These changes caused by the IDH1/2 mutations will eventually lead to the development of glioma. Immunized mice showed a higher number of peripheral CD8+ T cells, higher levels of IFN-gamma and anti-mIDH1 antibodies [49] These results indicate the potential of the vaccine in the treatment of glioma patients with IDH1 mutation.

I and II

Findings

CONCLUSIONS