BET Bromodomain Inhibition as Epigenetic Therapy in Pediatric Leukemia

New drugs are desperately needed for the treatment of pediatric leukemia. Leukemia is one of the most common and devastating cancers that can occur in children. While many infants and children diagnosed with acute leukemia can have durable remissions and even cures, the side effects of chemotherapy often lead to enduring harm to patients' health. Our research seeks to develop novel drugs for pediatric leukemia using a host of powerful genetic technologies, most notably, an approach called RNA interference screening. Our approach allows us to ask cancer cells "What proteins do you need to grow?" with as little bias as possible. Using this approach, we recently identified the protein BRD4 as an 'Achilles Heel' found in many forms of leukemia. Our current evidence suggests that new drugs, developed by our collaborators, that bind and inhibit BRD4 have remarkable anti-leukemia activity in experimental models.

In this proposal, we seek to explore the efficacy of BRD4-inhibitors in a broad collection of pediatric leukemia patient specimens. The overall goal of these efforts is to identify which pediatric leukemia patients are most likely to benefit from using these agents, such that these drugs can be introduced into clinical trials. The information obtained in this research proposal will have direct relevance to how these drugs are used in the pediatric leukemia patients in the clinic. Furthermore, I hope that funding through the ALSF will allow me to develop approaches for the study of pediatric cancer that can be utilized throughout my research career.