Challenge: Despite improvements in the treatment of many pediatric cancers, high-risk subtypes such as acute myeloid leukemia (AML) and acute megakrayoblastic leukemia (AMKL) still have amongst the worst prognosis, with only ~40-60% survival at 5-years. There is therefore a critical unmet medical need for novel targeted treatments but to completely eradicate the tumor cells these treatments will likely require combinations of drugs that may also be paired with immunotherapeutics. Lastly, to better track the course of patient treatment, new diagnostic technologies that are faster, cheaper, and more sensitive than current methods are needed.
Solution: The research team will fully characterize several antileukemic small molecules that were previously discovered to identify their targets, mechanism of action and validate their in vivo activity. They will extend these results by screening their human leukemia models against a proprietary collection of large macrocyclic molecules that can identify compounds capable of acting in synergy with their previously identified molecules. Lastly, the research team will exploit their custom leukemia biomarker antibodies to directly target leukemia cells while also powering a nanoscale electronic biosensor for leukemia detection.
Expected Achievements /Impacts: This project will allow the research team to move their most promising compound forward from a hit to a lead molecule, with a validated target and associated pharmacokinetic data, while also looking for synergistic drug activities. This project also includes building a full prototype biosensor that will have a wide range of biomedical, as well as generic, applications. The commercial partners will gain new products and services to offer along with new valuable internal expertise.