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 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 alternatives.