Abstract Relapsed Ewing sarcoma has dismal outcomes and has had minimal treatment advancements in the last 30 years - there is a critical need for the development of new treatments. The tumor is uniquely dependent on the oncogenic EWS::FLI1 fusion transcription factor to develop and maintain malignancy. Lurbinectedin is a small molecule analog of the natural product trabectedin that has shown efficacy in multiple cancers including Ewing sarcoma. The mechanism of toxicity of lurbinectedin in Ewing sarcoma is under investigation. Lurbinectedin exposure alters EWS::FLI1 trafficking into the nucleolus as measured by confocal microscopy. The subsequent impact of drug exposure on EWS::FLI1 binding to chromatin was determined by CUT Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4776.
Tolstyka et al. (Fri,) studied this question.