Glioblastomas (GBM) are highly invasive brain tumors that can spread rapidly throughout the brain. GBM are marked by a high rate of disease recurrence after therap. by virtue of the self-renewal capacity of glioma stem cells (GSCs), which are highly heterogeneous. Here, Thomas and colleagues identify a subset of GSCs bearing copy number alterations of the ASNS gene, leading to elevated expression of asparagine synthase. ASNS-high GSCs bore distinct metabolic features from other GSCs, including increased capacity for both glycolysis and oxidative phosphorylation and the ability to switch between them as needed in response to environmental cues. This metabolic plasticity allowed for rapid dissemination of ASNS-high GSCs throughout the brain tissue and a marked resistance to oxidative stress, rendering these cells de novo resistant to radiation. These findings nominate ASNS as a potential therapeutic target for GBM, which could restrict the pathogenicity of GSCs and enhance the efficacy of standard...

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