Project 460118

In Canada, approximately 1,400 children are diagnosed with cancer each year and approximately 30% of those have a brain tumor. Brain tumors are now the leading cause of cancer-related death in children under the age of 20 and medulloblastoma (MB) is the most commonly diagnosed childhood brain tumor. Although the average 5-year survival rate is between 70-85% for standard-risk MB cases using current radiation and chemotherapies, the long-term side effects suffered by MB survivors can be severe. There are an estimated 30,000 survivors of childhood cancer living in Canada with life-long health problems related to cancer treatments received as a child. To develop safer and more effective treatments for childhood cancers, we need to identify therapies that can target molecules that are unique to the cancer cells and do not harm healthy tissues. 'Oncogenes' are molecules that are abnormally activated in cancers that promote the uncontrolled proliferation of tumor cells. MYC is one of the most commonly dysregulated oncogenes across all cancer types and it is estimated that ~28% of tumors have abnormally high MYC expression. This includes MB, where high MYC expression is found in the most aggressive and lethal type of MB tumors. Hence, oncogenic MYC represents an attractive target for cancer therapy. However, there have been many technical and biological limitations that have prevented the development of MYC-targeting inhibitors for cancer therapy. We have uncovered a novel role for metabolism in maintaining the high expression of oncogenic MYC in MB tumor cells. Using this knowledge, we propose a new and unconventional strategy that uses metabolism-targeting agents to suppress oncogenic MYC expression. The goal of this project is to aid in the development of new metabolism-based treatment options for children suffering from highly aggressive MB brain tumors which may also have broad therapeutic implications for treating other MYC-driven tumors across the cancer spectrum.