Ewing sarcoma: historical perspectives, current state-of-the-art, and opportunities for targeted therapy in the future

Abstract

Purpose of review: As the second most common bone malignancy in children and adolescents, Ewing sarcoma family tumors represent almost 3% of pediatric cancers. Multidisciplinary management of patients with Ewing sarcoma has substantially improved the likelihood of survival for patients with localized disease. Yet, the prognosis of those with metastatic or recurrent disease has changed very little over the past three decades. Here, we focus on the current state-of-the-art in the diagnosis, staging, and treatment of Ewing's sarcoma and then highlight the most likely biological targets amenable to future therapies.

Recent findings: An improved understanding of the molecular biology of Ewing's sarcoma has led to clinical trials testing novel therapies specifically designed to thwart critical pathways responsible for this malignancy. Insulin-like growth factor-I receptor targeted monoclonal antibodies are just one example that has shown promise in early phase human clinical trials.

Summary: With an improved understanding of the genome, transcriptome, proteome, and other '-omic' events that promote and sustain Ewing pathogenesis, the use of nascent biologically targeted therapeutics is on the horizon. Understanding how and when to integrate such therapies into clinical practice, although challenging, may lead to a paradigm shift towards more personalized therapy.