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Researchers at the University of Michigan found that ZFTA-RELA fusion ependymoma (which make up most supratentorial ependymomas) tumor cells produce unusually high levels of itaconate, a substance normally made by immune cells. The tumor appears to use itaconate to help keep the ZFTA-RELA cancer-driving gene switched on, creating a cycle that helps the tumor grow. The researchers also found that the tumor changes the way it uses glutamine, a nutrient that helps provide the building blocks needed to make itaconate.
These discoveries have helped identify potential treatment targets. In mouse models, blocking either glutamine metabolism, the enzyme ACOD1 that makes itaconate, or related signaling pathways slowed tumor growth. Combining these treatments worked even better.
While this research is still preclinical, the University of Michigan team is now working with the Pediatric Neuro-Oncology Consortium (PNOC) to develop a clinical trial based on this research. We will keep an eye out and hope to see the trial open soon!