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Lastly, the heightened activity of the glucose monophosphate shunt results in excessive NADPH consumption, thereby depleting the cofactor necessary for the synthesis of glutathione (GSH)

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Given that HIF-2 is an important transcription factor in cancer progression and leads to poor prognosis 69,70 , these findings suggest that targeting HIF-2 might be an effective therapeutic strategy by inhibiting glutamine metabolism in these notorious cancers