Whether targeted agents that directly inhibit critical EWS/FLI protein-protein interactions or reverse the EWS/FLI transcriptional signature can successfully prevent or delay tumor progression remains as yet unanswered and will be the focus of the next generation of phase I/II trials, whose ultimate goal is to determine whether these novel therapies can significantly improve survival outcomes for patients with Ewing sarcoma. Here, EWSR1 is linked to Ewing sarcoma.