Article Text

  1. D. Berke
  1. Pomona, CA.


The Ewing family of tumors [EFT] (Ewing's sarcoma [ES] and peripheral neuroectodermal tumor [PNET]) are the second most common cancers in childhood and adolescence, and despite improvements in the treatment of these cancers with multi-agent chemotherapy, patients with recurrent disease, certain poor prognostic indicators, or suboptimal response to first line chemotherapy have few options for successful treatment of their disease and a low 5-year survival rate. Prior research established expression of the tyrosine kinase receptors c- kit and platelet-derived growth factor receptor-α (PDGFR-α) on EFT cell lines and the value of tyrosine kinase receptor inhibition in EFT with imatinib mesylate (Gleevec). The marine tunicate-derived agent ecteinascidin-743 (ET-743) has been found to be active in advanced, pretreated soft-tissue sarcoma and osteosarcoma in vitro and in vivo. This study sought to determine the therapeutic value of the combination of ET-743 and imatinib mesylate against EFT. Incubation with ET-743 for 4 hours in the ES cell lines, SK-ES-1, RD-ES, TC-71, and the PNET cell line, SK-N-MC showed cell death evident by light microscopy and reduced colony formation in clonogenic assays in all cell lines in a dose-dependent fashion. However, the combination of ET-743 and imatininib mesylate showed an antagonistic effect in the ES and PNET cell lines at all dose level combinations. These results suggest that ET-743 has cytoreductive anti-tumor activity in EFT, and warrants evaluation in clinical trials for patients with advanced ES and PNET. Further, caution should be exercised in evaluating the combination of ET-743 with a tyrosine kinase inhibitior in vivo. Additional investigation into the mechanism(s) underlying drug resistance encountered with this drug combination are warranted.

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.