The DNA minor groove-binding alkylating cytotoxic agent trabectedin is highly potent in vitro against Ewing sarcoma cells and other fusion protein-driven sarcomas, with direct modulatory effects on transcriptional targets of EWSR1::FLI1, yet has little to no single agent clinical activity (Baruchel [26]). The gene discussed is EWSR1; the disease is Ewing sarcoma.