Challenges in modeling EWS-FLI1-driven transgenic mouse model for Ewing sarcoma.

EWS-FLI1 is a master regulator of Ewing sarcoma (ES) oncogenesis. Although EWS-FLI1 represents a clear therapeutic target, targeted therapeutic inhibitors are lacking. Scientific literature has indicated accumulating information pertaining to EWS-FLI1 translocation, pathogenesis, function, oncogenic partnerships, and potential clinical relevance. However, attempts to develop EWS-FLI1-driven human-like ES mouse models or in vivo systems ended up with limited success. Establishing such models as preclinical screening tools may accelerate the development of EWS-FLI1 targeted therapeutic inhibitors. This review summarizes the current scenario, which focuses on the limitations, challenges, and possible reasons for past failures in model development and also plausible interim alternatives. AJTR