Translating BET Bromodomain Inhibitors for Acute Myeloid Leukemia Therapy
Background
Acute myeloid leukemia (AML) accounts for 20% of childhood leukemia and has a long-term survival of only 50%. Thus, new therapies are urgently needed. A new class of drugs, BET bromodomain inhibitors, target proteins that regulate the architecture of DNA and hold significant promise for treatment of pediatric leukemia. At the same time, the relevance of altered metabolism in AML has also come to the forefront. Much work is still needed to effectively implement these discoveries in the clinic.
Project Goals
Based on our preliminary data, in this proposal we will determine the effects of BET bromodomain inhibitors on metabolism in the cellular organelle called the mitochondria. For successful clinical implementation of BET bromodomain inhibitors, combinations of drugs will likely be needed as has uniformly been the case for curing patients with cancer. Thus, we will test combinations of compounds that alter cell metabolism with BET bromodomain inhibitors. Finally, it will be critical to develop assays to measure response to these drugs in early clinical trials. Our third aim focuses on the development and implementation of assays to measure individual patient response to BET bromodomain inhibitors to allow for personalized and thus more effective AML therapy.
