Elucidating Heterogeneity of Resistance Across Molecular Subgroups of Pediatric Ependymomas to Inform Future Therapeutics

Intracranial ependymomas are a common pediatric brain cancer. Advances in molecular profiling over the past decade have led to the identification of nine distinct molecular subgroups of ependymomas across three anatomical areas of the central nervous system. Radiation therapy, though effective at killing tumor cells, can cause major toxicities for patients and lead to the potential development of systemic resistance to subsequent therapies. It is still important to determine which molecular subgroups of ependymomas may benefit from post-radiation chemotherapy and which patients are resistant to post-radiation treatment. The central hypothesis of this research is that molecular subgroups of ependymomas acquire identifiable mutations following ionizing radiation exposure. Researchers believe this in turn contributes to the development of resistance to treatment. Researchers expect that the completion of this project will help elucidate the difference in response to radiation and chemotherapy across molecular ependymoma subgroups, informing future therapeutics. This project will involve the study of cell lines from each of the subgroups most common in children, specifically PF-EPN-A, STEPN- RELA, ST-EPN-YAP1. Ependymoma tumors are rare in children and ependymoma cell lines are difficult to establish, making the Children’s Brain Tumor Network provision of preclinical models particularly important to this work.