[Cancer therapy targeting tumor-induced neovascularization]

Neovascularization is critical for the growth of tumors and is mediated by physiological substances produced by the tumors. Vascular endothelial growth factor (VEGF) is one of such potent angiogenic factors. We evaluated VEGF gene expression on urinary bladder carcinoma and renal cell carcinoma by Northern blot analysis and demonstrated that VEGF was frequently overexpressed in renal cell carcinoma, in up to 67% of patients, but not in urinary bladder carcinoma. These results suggested that VEGF was produced by renal cell carcinoma and is responsible for the hypervascularity of this tumor. TNP-470, an angiogenesis inhibitor, is a new type of anticancer drug that inhibits tumor neovascularization. We evaluated the antitumor effect of TNP-470 in mice bearing B-16 melanoma or Lewis lung carcinoma. TNP-470 at a dose of 20 mg/kg body weight inhibited growth of both tumors. The degree of antitumor effect exerted by TNP-470 was greater than that of ADM (2.5 mg/kg body weight) and as great as that of MMC (2.5 mg/kg body weight). Combination of TNP-470 with MMC enhanced the antitumor effect. Monitoring of mouse body weight did not reveal any significant changes among the treatment groups, indicating that systemic toxicity of TNP-470 was not severe. These results suggested that TNP-470 was effective for the treatment of solid tumor by inhibiting its neovascularization.