Drugging the undruggable: early phase trial shows trabectedin and low-dose irinotecan downregulate EWSR1::FLI1 and has clinical activity in advanced Ewing sarcoma.

Targeting transcription factor fusion-positive cancers has proven challenging for decades. In SARC037, Grohar et al. show that histology-specific dosing of trabectedin and low-dose irinotecan is active in advanced Ewing sarcoma and downregulates EWSR1::FLI1 activity.