Grant: Project Grant

Medulloblastoma is the most common malignant brain tumor in children. Medulloblastoma is really made up of four diseases, of which one type, called Group 3 is highly aggressive and has a very poor outcome. The main tumor 'lump' in the brain is called the 'primary tumor'. The primary tumor can spread (metastasize) to cover other regions of the surface of the brain and spinal cord. When children die from medulloblastoma, it is mostly because the tumor has spread (metastasized). The most damaging therapies (radiation) for children with Group 3 medulloblastoma are necessary to treat the metastases. The dream of curing cancer through precision medicine has entailed sequencing cancers to identify tumor specific mutations, which could in turn be targeted by specific drugs that are lethal to the tumor but harmless to a child's normal cells. While this model is showing early success for some cancers, it holds limited promise for treatment of medulloblastoma. Recent results from the Ogilvie Lab have shown that Group 3 medulloblastomas appear to be driven by "control switches"-the factors that help choose which genes are turned on or off inside the cells. We want to know how one of these factors, called OTX2, controls other genes, interacts with other proteins, and regulates tumor growth both in a dish and when inside a patient. In addition, we also want to determine whether OTX2 plays different roles in medulloblastoma growth vs. normal development. Understanding how these control switches help make medulloblastomas grow, offers fresh opportunities to target Group 3 medulloblastoma, prevent the progression of metastases, and decrease the toxicity of therapy for children with this devastating disease.