Resistance to BET-bromodomain inhibitors in MYC-amplified medulloblastoma

Principal investigator: Pratiti Bandopadhayay, MD, PhD, Dana-Farber Cancer Institute
Award: $300,000 over three years
Co-mentors: Rameen Beroukhim, MD, PhD and Charles Stiles, PhD, Dana-Farber Cancer Institute

Twenty-five percent of all medulloblastomas are driven by a gene called MYC. This gene makes the tumors behave aggressively and they are frequently resistant to the current treatments. Dr. Bandopadhayay and Dr. Beroukhim have recently shown that a new group of drugs called BET-bromodomain inhibitors are a promising novel strategy to treat these tumors. They have found that models of medulloblastoma in the laboratory are sensitive to a BET-bromodomain inhibitor, JQ1, which was developed by Dr. James Bradner at Dana-Farber Cancer Institute. However, experience with other novel agents have shown that cancers frequently evolve to become resistant. If the resistance mechanisms are understood, new drugs can be added to overcome resistance. The goals of the project are to characterize the resistance mechanisms to BET-bromodomain inhibition in MYC-amplified medulloblastoma. The hope is the results will guide development of therapeutic strategies, including use of combination therapies, to improve the efficacy of BET-bromodomain inhibition for the children with MYC-amplified medulloblastoma.