Abstract IA010: Pediatric Low-Grade Gliomas Repurpose Neuron-OPC Dependencies to Control Tumor Growth

Abstract Pediatric low-grade gliomas (pLGGs) represent the most common brain tumors in children. While these slow-growing neoplasms rarely result in increased mortality, they are associated with significant morbidity, including weakness, visual decline, balance/walking difficulties, and behavioral changes. Pioneering studies over the past decade have revealed that these tumors are characterized by increased RAS/ERK activation. However, these tumors are highly dependent on cells and signals from their local brain microenvironment and often undergo premature senescence in tissue culture. Studies from our laboratory using primary patient pLGG cell lines, 3D pLGG-organoids, and patient-derived xenografts in Cxcl10-null mice have demonstrated that one etiology for this striking stromal dependency is the requirement for neuron-derived neurotransmitter support. Specifically, we found that neurons elaborate glutamate to stimulate pLGG tumor growth through glutamate receptor activation of the platelet-derived growth factor receptor (PDGFRa) tyrosine kinase receptor (RTK) and increased MEK/ERK mitogenic signaling in vitro and in vivo. The use of these avatars to explore neuronal regulation of pediatric brain tumor growth will be presented with a particular focus on the molecular mechanisms that underlie this unique stromal dependency. Citation Format: Corina Anastasaki, Enquan Xu, Chloe Kernan, Yuqing Gao, Christina Zhang, David H. Gutmann. Pediatric Low-Grade Gliomas Repurpose Neuron-OPC Dependencies to Control Tumor Growth abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (6Suppl): Abstract nr IA010.