Regulation of apoptosis and proliferation in Ewing's sarcoma--opportunities for targeted therapy

The Ewing's sarcoma family of tumors are malignant tumors of bone and soft tissue which occur predominantely in children and adolescents. Whereas cure rates for patients with localized tumors are around 70%, survival rates for patients with metastases or relapse are poor in spite of intensive chemo- and radiation therapy, demonstrating a clear need for new, more effective therapies. Insights into the biology of the tumors of the Ewing's sarcoma family with identification of the EWS/ETS gene rearrangement as the key event in malignant transformation and its influence on the regulation of various pathways involved in proliferation, differentiation and apoptosis has led to the identification of potential targets for the development of new molecular therapeutics. This review will focus on the regulation of major pathways of proliferation and apoptosis in tumors of the Ewing's sarcoma family and point out how modulation of these pathways might be of potential use for future therapy.