Uncovering the molecular targets of a novel MYC inhibitor for medulloblastoma
Mentor: Robert Wechsler-Reya
Medulloblastoma is the most common malignant brain tumor in children. Even with aggressive treatment (surgery, radiation and chemotherapy), many medulloblastoma patients die of their disease, and survivors suffer severe long-term side effects from therapy. Safer and more effective therapies for medulloblastoma are desperately needed, and discovering them depends on understanding and targeting the proteins that drive the disease.
One key driver of medulloblastoma is a protein called MYC. In normal cells, MYC functions to regulate cell growth and proliferation, but when MYC levels are too high, cells cannot stop growing, and cancer may ensue. MYC is found at exceptionally high levels in medulloblastoma, as well as in cancers of the blood, lung, breast and prostate, and there has long been interest in developing drugs to target it. We recently identified a potent MYC inhibitor, and are working to develop it into an anti-cancer drug.
To optimize the compound’s activity, we need to understand how it works. Previous studies suggest that the compound does not target MYC directly, but rather, acts on enzyme that regulates MYC levels. The major goal of the POST program project is to determine whether the MYC-targeting compound works by inhibiting this enzyme. These studies will help the lab generate more potent and more effective MYC inhibitors. If these inhibitors can be developed into drugs, they could have a major impact on the survival and quality of life of patients with medulloblastoma.
