Ependymomas (EPN) are central nervous system (CNS) tumors that occur in children and feature a 50% 10-year survival rate. Surgical resection and radiation are standard of care; however, many children develop recurrences that require multiple surgeries and come with a dismal prognosis. Children that do survive, can suffer significant neurological deficits caused by these aggressive and grueling interventions. Critically, the standard of care for EPN has not changed in over 30 years, highlighting the dire need to develop new, targeted therapies for children afflicted with this malicious disease. Recent advances in the burgeoning field of "Cancer Neuroscience" highlight how resident neurons in...

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Ependymomas (EPN) are central nervous system (CNS) tumors that occur in children and feature a 50% 10-year survival rate. Surgical resection and radiation are standard of care; however, many children develop recurrences that require multiple surgeries and come with a dismal prognosis. Children that do survive, can suffer significant neurological deficits caused by these aggressive and grueling interventions. Critically, the standard of care for EPN has not changed in over 30 years, highlighting the dire need to develop new, targeted therapies for children afflicted with this malicious disease. Recent advances in the burgeoning field of "Cancer Neuroscience" highlight how resident neurons in the brain interact with brain tumors and how these interactions play an essential role in promoting tumor progression and recurrence. How neurons influence EPN tumorigenesis is currently unknown, and, in this application, we will decipher how these mechanisms influence EPN tumor growth. In addition, applying these principles of Cancer Neuroscience to EPN we have generated compelling preliminary data that points to a new therapeutic intervention for treating children with EPN tumors. Critically, these approaches are currently used to treat patients with multiple myeloma and could be readily translated to patients with EPN. Therefore, this application will focus on three goals. First, we will uncover how neuronal activity influences gene expression programs within EPN tumors. Second, we will determine how a key regulator of these gene expression patterns influences EPN tumor growth. Third, we will decipher whether a newly identified therapeutic intervention effectively blocks the growth and progression of EPN tumors in a variety of mouse models. We anticipate that our project will open the door for a new understanding of how neuronal activity influences EPN tumor progression, while bringing our studies into the realm of translational cancer neuroscience.

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