Epigenetic and Transcriptional Signaling in Ewing Sarcoma-Disease Etiology and Therapeutic Opportunities

Ewing sarcoma (EwS), a type of bone and soft tissue tumor, is mainly driven by the expression of the fusion protein EWSR1-FLI1. Upon binding to chromatin, EWSR1-FLI1 reprograms the epigenetic state, alters gene expression, and thus leads to tumorigenesis. Considerable studies have investigated the epigenomic and transcriptomic profiling of EwS. Nevertheless, a comprehensive view of therapeutic targets is still lacking. This review discusses the epigenetic and transcriptional alterations reported in EwS. Specifically, we discuss the binding characteristics of EWSR1-FLI1 on chromatin, the mechanisms of EWSR1-FLI1 in reprograming epigenome, and EWSR1-FLI1-induced transcriptional alterations. Moreover, we summarize the chemical, RNAi, and CRISPR-cas9 high throughput screens conducted in EwS with the goal of assisting in the development of novel therapies to treat this aggressive disease.

Automated summary

This review discusses the epigenetic and transcriptional alterations in Ewing sarcoma and summarizes the relevant screening studies conducted to develop novel therapies.