Past, present and future of therapies in pediatric sarcomas

Abstract

Limited progress has been made over the past 30 years in improving the outcome of patients with high-risk pediatric sarcomas. The 5-year overall survival rate remains at 20% or less with metastatic sarcomas. Therefore, current and future research is focused on the identification and development of molecular or biological agents targeting the pathogenic pathways in sarcomas, either alone or in combination with conventional chemotherapy. To this end, the most promising activity has been seen with IGF-1 receptor antibodies and mTOR inhibitors. Other agents of interest are oncolytic viruses, epigenetic modulators (e.g., histone deacetylase inhibitors), immune modulators (e.g., muramyl tripeptide phosphatidylethanolamine) and other biological agents (e.g., trabectedin). In addition to the development of novel drugs, the other major area of recent focus is developing immune therapies, such as dendritic cell vaccines and adoptive immunotherapy for treating pediatric sarcomas. This article discusses the successes, the failures and the future direction of these therapies.