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Ewing sarcoma is a devastating childhood bone cancer. Doctors treat these pediatric patients with toxic chemotherapies, radiation, and surgery. Dr. Langdon and colleagues will develop targeted combination therapies to safely and effectively kill Ewing sarcoma cells. Dr. Langdon finds changing where proteins are normally found in cancer cells create potential new targetable vulnerabilities for Ewing sarcomas. Each vulnerability is thought of as a new "Achilles heel" for these cancers. Dr. Langdon and colleagues believe that combining two drugs - one which changes where proteins are normally found and one which targets the new vulnerability - will kill Ewing sarcomas. Dr. Langdon's team will look to why these drugs work so well against Ewing sarcomas and determine if they are truly safe and effective.