Grant: Project Grant

Brain tumors represent the leading cause of childhood cancer mortality, due to their highly aggressive and often incurable nature. Medulloblastoma (MB), the most common malignant pediatric brain tumor, comprises four subgroups (Wingless (Wnt), Sonic Hedgehog (Shh), Group 3, and Group 4) that are defined by the expression of unique sets of genes. Clinically, Group 3 MB (G3MB) patients are characterized by metastatic disease, increased rates of recurrence, and poor overall survivorship. The latter underscores an urgent need to develop novel therapies for children with Group 3 MB. Using a genetic engineering technology known as CRISPR, we identified a gene involved in metabolism as potential drug target for therapy development in MB. Here we propose a campaign to elucidate how this change in cellular metabolism fuels Group 3 MB initiation disease progression. We will use specialized equipment capable of measuring metabolism in MB tumor cells and healthy, non-tumor cells to learn how blocking this metabolic pathway leads to death of MB tumor cells. Achievement of these research objectives will allow us to identify novel treatment strategies for Group 3 MB, in addition to increasing our ability to stratify patient risk.