EWSR1 and Ewing sarcoma: Numerous biological pathways, such as those involving insulin-like growth factor receptor (IGFR), platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), Sonic HedgeHog (SHH) pathway activation, Wnt, and transforming growth factor (TGF)-β receptor II pathway inhibition, are modulated by EWS-FLI1 activity, leading to proliferation, angiogenesis, immune system escape, metastatic potential, and treatment resistance that contribute to the Ewing sarcoma malignant phenotype (11).