Blocking Brain-Tumor Angiogenesis Extends Survival in Rat Model

Cancer researchers have used miniature osmotic pumps to deliver drugs that block tumor angiogenesis in a rat model of human brain cancer (glioblastoma).

Investigators from the Medical College of Wisconsin (Milwaukee, WI, USA) had shown previously that the enzyme cytochrome P450 2C11 epoxygenase (CYP epoxygenase) was linked to angiogenesis in the brain. In the current study, they sought to determine if inhibition of CYP epoxygenase would be effective in reducing capillary formation in glioblastoma with a concomitant reduction in tumor volume and increase in animal survival time.

To this end, the investigators compared three sets of rats that harbored transplanted human glioblastomas. The two test groups were treated with one of two inhibitor drugs, 17-ODYA or miconazole, to block the fatty acid CYP epoxygenase, and the control group received a placebo. Drugs were infused directly into the tumors over an extended period, using specially designed miniature osmotic pumps.

Results published in the August 2008, Journal of Cerebral Blood Flow & Metabolism revealed that compared to the control group, tumor size in the drug-infused groups was reduced by an average 50-70%, and survival time increased by five to seven days, equivalent to three to four months in terms of human survival.

"These rat model tumors were developed from human glioblastoma tumor cells and closely mimic human tumors in growth patterns and response to therapy,” explained senior author Dr. David Harder, professor of physiology at the Medical College of Wisconsin. "The concept of targeting blood vessels that feed tumors as an approach to limit tumor growth is not a novel idea. However, blocking the specific fatty acid described in this study is novel, and holds great promise for use in humans. If survival time could be extended, with a combination of surgical therapy and infusion with similar drugs, this could be a significant treatment option.”

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