INHIBITION OF WILMS TUMOR XENOGRAFT PROGRESSION BY HALOFUGINONE IS ACCOMPANIED BY ACTIVATION OF WT-1 GENE EXPRESSION

ABSTRACTPurpose:: Wilms tumor (WT) is the most common malignant neoplasm of the urinary tract in children. Although it is curable with long-term survival, the combination of surgery, chemotherapy and often radiotherapy in some cases results in severe complications in adulthood. Therefore, novel therapeutic strategies that would decrease treatment burden and improve outcome for high risk patients are required. We evaluated the efficacy of halofuginone, an inhibitor of collagen type I synthesis and angiogenesis, to inhibit WT development in xenografts models.Materials and Methods:: WTs derived from 2 patients with favorable histology at different disease stages were implanted subcutaneously or orthotopically in the kidneys of nude mice. Halofuginone was administered intraperitoneally (2 μg per mouse every other day) or given in the diet (1 part per million).Results:: Independent of disease stage, tumor location or administration route, halofuginone caused a decrease in angiogenesis that resulted in marked i...