Background

Ewing’s sarcoma is the second most common pediatric bone tumor with a poor overall survival rate. This tumor depends on the continued activity of the EWS-FLI1 transcription factor to maintain the malignant phenotype. Silencing of EWS-FLI1 is incompatible with the continued proliferation of Ewing’s sarcoma cells and places the cells in a de-differentiated state that clusters with mesenchymal stem cells by principle component analysis. We have previously shown that treatment of Ewing’s sarcoma xenografts with trabectedin in combination with irinotecan leads to the differentiation and replacement of the tumor with fat; an effect that can be modeled in vitro.