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Researchers from the University of Michigan have reported a new metabolic vulnerability in pediatric ependymoma, a common childhood brain tumor that remains incurable with current therapies. Standard treatment today is maximal surgical resection followed by radiation, with chemotherapy offering limited benefit and no approved targeted therapies. In this new study, the investigators showed that most supratentorial ependymomas driven by the ZFTA-RELA fusion protein depend on production of itaconate, a metabolite usually made by immune cells. They found that tumor cells generate itaconate via the enzyme ACOD1, and that itaconate and ZFTA-RELA form a feed-forward loop that promotes tumor growth through glutamine metabolism. Blocking this pathway reduced fusion protein levels and shrank tumors in mouse models, providing the first evidence that ZFTA-RELA-driven ependymomas can be targeted indirectly. The researchers are now working with the Pediatric Neuro-Oncology Consortium (PNOC) to develop a clinical trial targeting the itaconate pathway.