Nov. 25, 2003 Combining radiation with an agent that blocks VEGF, a protein that promotes the development of blood vessels and the growth of cancerous tumors – a process known as angiogenesis – may be more effective against brain tumors than either treatment alone, researchers at Jefferson Medical College have found.
Scientists led by Phyllis Wachsberger, Ph.D., assistant professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and Adam Dicker, M.D., associate professor of radiation oncology at Jefferson Medical College, looked at whether adding radiation changed the effectiveness of a drug called VEGF Trap on the growth of a common brain tumor, glioblastoma, in a mouse model. VEGF Trap is a protein engineered to block VEGF activity. The particular type of brain tumor expresses high levels of VEGF and is resistant to treatment with many other antiangiogenic drugs.
According to Dr. Dicker, who is also director of the Division of Experimental Radiation Oncology at Jefferson's Kimmel Cancer Center, the findings indicate that radiation may in many cases substantially enhance the drug's anti-tumor activity. In fact, research results from Jefferson and other laboratories indicate that VEGF Trap may be as much as 1,000 times more potent in controlling cancerous tumor growth than angiogenesis inhibitors now under review by the Food and Drug Administration, he says.
Dr. Wachsberger presents the group's work November 19 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.
"These are the first studies showing a potential benefit of this agent and radiation," Dr. Dicker says.
The scientists compared the effects of both small and large doses of VEGF Trap on tumor growth in mice that either had or didn't have radiation treatments. In the study, radiation alone delayed tumor growth for 10 days more than control mice, to which no treatment had been given. Radiation plus low-dose VEGF Trap increased the growth delay by 20 to 25 days more than the control. High-dose VEGF Trap did even better, adding an extra 40 days of growth delay, though in this case the researchers didn't see any benefit from adding radiation.
Next, says Dr. Dicker, the Jefferson group hopes to refine the use of radiation with VEGF Trap, including getting a better idea of specific doses and their timing and effectiveness.
Regeneron Pharmaceuticals, Inc., in Tarrytown, NY, funded the research.
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