Investigational therapies for Ewing sarcoma: a search without a clear finding

Introduction: Ewing sarcoma family tumors (ESFT) are a group of aggressive diseases, characterized histologically by small, round, blue cells and genetically by translocation involving EWS and ETS partner genes. The current treatment of localized Ewing sarcoma (ES) requires a multi-disciplinary approach, including multidrug chemotherapy, administrated before and after local treatment, surgery and radiation therapy. Unfortunately, the cure rate of metastatic or refractory/recurrent disease is still very poor. Areas covered: In this review, the authors summarize the new types of therapy and strategies aimed to improve the prognosis or cure ES. Herein, the authors discuss several preclinical and phase I-II studies with new-targeted therapies. The most studied therapies are insulin-like growth factor receptor (IGF1R) inhibitors but have limited efficacy. Other strategies include Mammalian Target of Rapamycin (mTOR) Inhibition, poly ADP ribose polymerase (PARP) inhibition, vascular endothelial growth factor (VEGF) inhibition, tyrosine kinase inhibitors and telomerase inhibitors, all with limited effectiveness. Expert opinion: Future treatment strategies should combine one or more targeted therapies with conventional chemotherapy. Some combined modality treatments are under clinical study. However, treatment breakthroughs are still needed to improve the relatively poor prognosis of recurrent/metastatic ESFT.