BRD4 as a Therapeutic Target for Medulloblastoma

Award: $150,000
Project leader: Rameen Beroukhim, MD, PhD, Dana-Farber Cancer Institute
Funding Partner: Christopher Brandle Joy of Life Foundation

In approximately 25 percent of medulloblastoma cases, tumor growth is driven by the amplification of a gene called MYC. The majority of children with MYC-amplified medulloblastoma die of their disease. Other pediatric cancers that harbor amplifications of MYC family members, notably neuroblastoma, are also similarly associated with devastating outcomes. Novel therapeutic strategies are desperately needed in the clinic for children with these cancers. Experience with novel agents, however, has shown that cancers frequently evolve to become resistant. A promising therapeutic approach is to develop combination treatments that include drugs to overcome or circumvent the development of resistance. In laboratory studies, Dr. Beroukhim has shown that MYC- amplified medulloblastomas are sensitive to a class of chromatin modifiers called BET-bromodomain inhibitors. The specific aims of his proposal are to fully elucidate the mechanism of action of this family of inhibitors and thereby gain insight into the genes and proteins that confer resistance. His results will guide strategies to optimize the efficacy of BET-bromodomain inhibitors for children with MYC-amplified medulloblastoma and provide a framework to study cancer’s evolution in response to this novel class of cancer drugs.