Isocitrate dehydrogenase 1–mutated human gliomas depend on lactate and glutamate to alleviate metabolic stress

What is it about?

Gliomas are primary brain cancers that are characterized by extreme invasion into the brain tissue, making curative surgery impossible. This behaviour is not found in other types of brain cancer and in brain metastases. The underlying cause is not understood. Many of these cancers are characterized by mutations in isocitrate dehydrogenase, an enzyme that is centrally involved in metabolism. To get more insight in the consequences of these mutations for biological behaviour, we here studied metabolism in these cancers and found that IDH mutated cancer cells heavily depend on glutamate and lactate, metabolites produced by normal brain cells. This can explain the diffuse character of these tumors, but may also point at specific metabolic pathways, inhibition of which might have a therapeutic effect for these untreatable cancers.

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