Funded by the Dick Vitale Pediatric Cancer Research Fund with support from the Marc and Peg Hafer Family
Acute myeloid leukemia (AML) remains one of the most difficult leukemias to treat. Pediatric patients with AML have relied on standard toxic chemotherapy and bone marrow transplantation for the past few decades for treatment without any advancement in the development of targeted therapeutics for this disease. The development and clinical investigation of a new class of orally available drugs, called Menin inhibitors, has shown great promise in patients with specific, hard-to-treat subtypes of AML. However, we have recently described acquired resistance to Menin inhibitors through genetic mutation in the Menin gene during treatment. After characterizing and understanding the mutations in Menin, we now aim to try to overcome and possibly prevent resistance with the next generation of Menin inhibitors or with combinations with other drugs that show promise in treating AML. The experiments proposed here will guide the clinical implementation of Menin inhibitors into the standard of care in children with either newly diagnosed or refractory AML. We hope/expect that these approaches will, over time, supplant the need for chemotherapy much as has been the case for targeted therapy in APML, which previously required bone marrow transplantation, but is now cured with two oral therapies that have minimal toxicities.