Abstract SY06-01: Neuronal regulation of brain cancers

Abstract In the central nervous system, neuronal activity is a critical regulator of development and plasticity. Concordantly, neuronal activity robustly promotes progression of both high-grade and low-grade glioma subtypes in preclinical models. Crucial mechanisms mediating activity-regulated glioma growth include paracrine secretion of BDNF and the synaptic protein neuroligin-3 (NLGN3). NLGN3 induces multiple oncogenic signaling pathways in the cancer cell, and also promotes synapse formation between neurons and glioma cells. Glioma cells integrate into neural circuits through neuron-to-glioma synapses that exhibit mechanisms of malignant synaptic plasticity and a diversity of synapse types. This synaptic and electrical integration of glioma into neural circuits is central to tumor progression in preclinical models. Thus, both paracrine and synaptic neuron-glioma interactions play important roles in the pathogenesis of glial cancers, highlighting a number of potential therapeutic opportunities. The subversion of mechanisms of neurodevelopment and plasticity by malignant gliomas underscores the importance of understanding the neuroscience of brain cancer. Similar mechanisms of neuron-cancer interactions are increasingly appreciated in brain metastases and in cancers outside of the CNS; nervous system-cancer interactions are now emerging a new hallmark of cancer. Citation Format: Michelle Monje. Neuronal regulation of brain cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr SY06-01.