Funded by Matthew Ishbia and the Dick Vitale Pediatric Cancer Research Fund
Childhood cancers of developing muscle are some of the most difficult to treat childhood cancers. Therapy has not significantly changed in the past 20 years and there isn’t even a meaningful new treatment being considered. Currently, even after the most intensive therapy possible, a third of these tumors will return and take the life of a child or young adult. We have taken a new approach using state-of-the-art methods to identify what we hope will be more targeted and less toxic treatments that yield better outcomes. We have already identified three new therapeutic avenues that we will test. The first is to ask if the abnormal gene that drives this disease, called PAX3-FOXO1, is a good drug target. We engineered the gene to be sensitive to a derivative of a known drug. While we can’t do this in kids, it allows us to ask what would happen if we had a drug? Second, we found that PAX3-FOXO1 turns on a small number of other genes, and we already have drugs that can target some of these. Third, we identified other possible drug targets that PAX3-FOXO1 recruits. We will test if these are key to causing cancer and if they would be good drug targets. We believe that our comprehensive approach gives us the best chance in the past 30 years to change the lives of these children with cancer, and to identify drugs or drug combinations that will be less toxic and yield better outcomes for these patients.