Michael Jackson (SBP)
Lukas Chavez (MCC)
Brain and other tumors of the central-nervous system (CNS) are the most common cancers in children aged 0- 14 years in the USA. Ependymoma (EPN) is the third most common pediatric brain tumor and a leading cause of death in childhood cancer patients. The most common and aggressive subgroup, posterior fossa ependymoma group A (PFA), occurs mainly in young children and frequently leads to recurrences. Here we propose to screen patient derived PFA EPN samples with drugs already approved by the FDA for various other conditions and diseases. These compounds are safe to administer to humans and as such provide the quickest path to identifying drugs that could be rapidly deployed to ependymoma patients in the medium term. We will prioritize drugs that can access the brain and will test for agents that are effective only against ependymoma, and not normal healthy brain cells, to avoid eventual toxicity. Once active drugs have been identified we will also investigate their mechanisms of action. By investigating changes in gene expression after treatment we will identify specific genes and downstream pathways that are involved in cell death and survival of ependymoma cells, potentially allowing further targeting of this deadly childhood disease.