Investigating the metabolic vulnerability in glioma

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We have elucidated that the NRF2-guided antioxidant pathway plays a critical role in the metabolic adaptation of IDH1-mutated glioma during oncogenesis. Notably, de novo glutathione biosynthesis is upregulated to mitigate the oxidative stress induced by mutant IDH1 activity. In addition, we observed substantial mitochondrial reprogramming in these tumors, with a shift toward maintaining redox homeostasis. To further dissect the mitochondrial pathways essential for the survival of IDH1-mutated glioma, we developed a custom guide RNA library for an unbiased genetic screen. The library is performing optimally, and the formal screening is currently underway.