Molecular Changes Associated With Tumor Initiation and Progression of Soft Tissue Sarcomas: Targeting the Genome and...

Soft tissue sarcomas are rare, but generally aggressive tumors which disproportionately affect children and young adults. They represent less than 10% of all cancers, but are one of the most frequently diagnosed cancers in pediatric patients. These cancers have a high rate of morbidity and mortality, and their overall incidence has been increasing at an estimated rate of 26% over the last 2 decades. The cause of this increased incidence is unknown but various environmental factors have been implicated. Establishing standard therapeutic strategies is challenging for soft tissue sarcomas as more than 50 different histological subtypes exist, each with their own molecular alterations and clinical characteristics, and this combination of tumor heterogeneity and a limited number of clinical cases make detailed omics level molecular studies particularly challenging. This chapter will focus on the unique genetic and epigenetic changes which characterize these cancers, with an emphasis on translocation-associated sarcomas involving primary gene fusions with the RNA chaperone protein EWSR1. We will highlight current therapeutic approaches and discuss opportunities for targeted molecular therapeutics.