New Drug Shuts Off Tumor Blood Supply

A new drug created by linking a vascular endothelial growth factor, VEGF, to a genetically engineered toxin, rGelonin, has been shown to selectively destroy blood vessels supplying solid tumors without harming the blood vessels supplying normal tissue. The findings were reported in the June 11, 2002, issue of the Proceedings of the National Academy of Sciences.

Researchers from the University of Texas M. D. Anderson Cancer Center (Houston, USA) chose the genetically engineered toxin rGelonin to link to the VEGF carrier because it does not appear to be antigenic in human clinical trials and does not cause damage to normal blood vessels, as do other toxins that have been explored for use in antitumor therapies. VEGF plays a key role in the growth and metastasis of solid tumors by mediating the creation of new blood vessels required by the tumor to maintain growth and metastasize.

Mice were injected with human melanoma and prostate cancer cells, and then some were treated with VEGF/rGel. Tumor growth in the mice that received the drug was reduced to 16% of that of the untreated mice. Destruction of the tumor blood vessels was observed as early as 48 hours after administration of the VEGF/rGel, and there was no apparent damage to any normal organs, including the kidneys, of the treated mice. Attacking tumors by restricting their ability to generate new blood vessels is a way to circumvent the ability of the tumor cells to mutate and develop drug resistance.

"The significance of this fusion toxin is that it is not specific to one kind of tumor. It has impressive antitumor effects in various kinds of tumors, including melanoma and prostate cancers,” said Dr. Michael Rosenblum. "We need additional research to determine if it is equally effective in other cancers.”



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