Validating candidate combination therapies for Ewing sarcoma
Mentor Name: Brian Crompton
Ewing sarcoma is the second most common bone cancer in children. Although cure rates in children with localized disease approach 75%, treatment has significant toxicity. Furthermore, standard therapies are largely ineffective in the treatment of patients with metastatic or recurrent disease. New and less toxic treatment approaches are needed for patients with Ewing sarcoma. In previous award cycles, we identified two protein dependencies in Ewing sarcoma, focal adhesion kinase and aurora kinase B, that can be inhibited with experimental drugs. However, the drugs targeting these proteins have been slow to achieve approval for cancer and remain inaccessible for testing in pediatric clinical trials. As a result, we have broaden our approach to identifying additional drug targets and drug combinations for validation as candidate therapeutic strategies for Ewing sarcoma. In this application, we propose to validate multiple drug combinations, this time of approved anti-cancer drugs, identified from a large high-throughput screen. We believe these studies will identify and validate new therapeutic approaches that could be more rapidly translated to the clinic for patients with Ewing sarcoma.
