Grant: Project Grant

Cancer is the leading cause of death related to diseases in Canadian children, with brain tumors being the most dangerous. Among these, medulloblastoma (MB) is the most common brain cancer in kids. Studies have shown that the most aggressive form of MB, known as Group 3 (G3), starts from immature cells in a part of the brain called the rhombic lip. However, scientists still don't fully understand why these cells don't develop normally and instead turn into cancer. Recent research suggests that the way cells use energy (metabolism) is linked to how certain proteins and genes behave in cancer. However, we don't yet know how metabolism affects the identity of the aggressive G3 MB cells. We believe that metabolism plays a key role in stopping these cells from growing up properly and becoming cancerous. In our proposal, we have discovered that aggressive G3 MB cells are highly active in a process called lactate metabolism. We found a new connection between this process and a protein called OTX2, which is important for keeping these cells in their immature state and making the cancer worse. OTX2 increases lactate metabolism, and lactate helps to keep OTX2 stable, creating a cycle that drives the disease. In this project, we will study how OTX2 and lactate metabolism work together in G3 MB cells and how the OTX2-lactate connection controls the cancer's behavior. We will test whether targeting lactate metabolism can be a new treatment for G3 MB. We will run pre-clinical trials using brain tumor animal models to see if blocking this process, alone or with current treatments, can help fight the disease. There are currently no approved targeted therapies for G3 MB. By understanding the specific events that lead to the development and progression of G3 MB, our research could lead to new, much-needed treatment options for this deadly cancer.