SUPPRESSION OF RHABDOMYOSARCOMA GROWTH BY FUMAGILLIN ANALOG TNP-470

The purpose of our study was to investigate a novel therapeutic approa ch for rhabdomyosarcoma (RMS) in an animal model. The pursuit of new t herapeutic modalities for RMS is critically important since this type of tumor is the most common soft tissue sarcoma in children and becaus e patients with metastatic disease may not be cured with current thera peutic modalities. We studied whether RMS growth may be suppressed by TNP-470, an analog of fumagillin, which was found to inhibit neoangiog enesis. Our data had shown that animals treated with TNP-470 (60 mg/kg ), over a specific period of time, had approximately 50% smaller tumor s than controls. Consistent with previous observations, treatment with TNP-470 decreases the level of the cyclin DI. Tumors dissected from T NP-470-treated animals had also considerable necrotic areas. In additi on, TNP-470 had a direct cytotoxic effect on RMS cells in vitro. Our s tudy has shown, therefore, that RMS in an animal model and in vitro re sponds to treatment with TNP-470, which suggests that the inhibitors o f angiogenesis may be useful in a novel therapeutic design for RMS. (C ) 1996 Wiley-Liss, Inc.