Characterizing Resistance Mechanisms to BET-Bromodomain Inhibition in MYC-amplified

Background:

Medulloblastoma is the most common malignant brain tumor of childhood. A particularly aggressive subtype of medulloblastoma is characterized by increased copies of the cancer causing gene called MYC. Indeed, one quarter of all medulloblastomas are MYC-amplified. Recently, we have found that a new group of drugs called BET-bromodomain inhibitors can “turn off” this gene and suppress growth of models of the tumor in the laboratory. These drugs are now entering clinical trials, but our experience with other cancer treatments has been that tumors will learn how to resist these drugs over time.

Project Goal:

In this project we will study how medulloblastoma cells may develop resistance to these drugs. By studying this, we hope to determine ways to overcome such resistance to increase the effectiveness of these drugs in treating children with this aggressive disease