The Goldilocks paradox: when partial oncoprotein inhibition fuels metastasis in Ewing sarcoma

Targeting oncogenic fusion proteins remains a major challenge in pediatric oncology. In this issue of EMBO Molecular Medicine, Suresh et al (2025) demonstrate that incomplete inhibition of EWS::FLI1 in Ewing sarcoma paradoxically promotes metastatic behavior, revealing critical implications for therapeutic strategies. JY Blay & colleagues discuss the study by Suresh et al, in this issue of EMBO Mol Med, that shows that incomplete inhibition of EWS::FLI1 in Ewing sarcoma paradoxically promotes metastatic behavior.