Low-grade brain tumors (gliomas) are among the most common cancers in children. While pediatric low-grade gliomas (pLGGs) are rarely fatal, they can cause life-long weakness, vision loss, balance/walking difficulties, and changes in behavior. Unfortunately, our current treatment options include cytotoxic medications used for malignant tumors or molecularly targeted therapies (MEK inhibitors), which are often limited by difficulties with patient tolerance and adverse drug effects. To identify alternative therapies, our laboratory has pioneered the development of novel models of pLGG using pLGG cells isolated from tumors removed in the operating room as part of routine medical care, human pLGG mini-brains (organoids), and mice harboring human pLGG tumors. Using these platforms, we have shown that pLGG cancer cells require supportive signals from nerves in the brain and that blocking these signals using medications now in use for epilepsy and mood disorders in children reduces pLGG growth in mice. Based on these exciting observations, we hypothesize that pLGGs actively recruit nerves in the brain to establish functional connections that control tumor growth. In this proposal, we will directly investigate the mechanism by which pediatric LGG tumor cells attract nerves and define these nerve-cancer connections as a first step towards identifying new treatment approaches for pediatric brain tumors.