Exploiting iron metabolism in Ewing sarcoma

Ewing sarcoma is an aggressive bone cancer of children and young adults. Survivors face long-term complications from intensive chemotherapy and outcomes remain stubbornly poor for patients with metastases. There is an urgent need for improved treatments. Emerging evidence suggests Ewing sarcoma is particularly sensitive to perturbed iron homeostasis. As iron contributes to many critical processes, there are multiple mechanisms to disrupt iron metabolism. Several pre-clinical studies exploiting altered iron homeostasis in Ewing sarcoma report encouraging results. This review summarizes unique features of and ways to target iron metabolism in Ewing sarcoma, and the translational potential for these therapeutic strategies. Hayes and Theisen review the role of altered iron metabolism in Ewing sarcoma biology. They discuss preclinical strategies targeting this vulnerability that show promise for clinical translation, including approaches aimed at STEAP1/2, IL1RAP, iron-sulfur cluster proteins, and iron chelation.