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Timing appears essential to combining antiangiogenesis and radiation therapy

Although the earliest clinical trials of the cancer-fighting potential of antiangiogenesis drugs did not have the dramatic results that some hoped for, subsequent trials showed that combining agents that suppress blood-vessel growth with therapies that destroy cancer cells can improve patient survival. In the December issue of Cancer Cell, researchers from the Massachusetts General Hospital (MGH) describe how timing may be crucial to successfully combining angiogenesis inhibitors with radiation treatment and reveal more about exactly how these drugs work to fight cancer, which is somewhat different from earlier theories.

"The blood vessels that develop to supply nutrients to a tumor are not normal," says Rakesh Jain, PhD, director of the Steele Laboratory in the MGH Department of Radiation Therapy, the study's senior author. "The vessels are leaky, dilated, disfigured, and do not evenly inflitrate the tumor, which can interfere with standard cancer therapies. Chemotherapy drugs are not distributed throughout the tumor, and the oxygen level is low, making tumors resistant to radiation therapy. It now appears that antiangiogenic therapy transiently improves a tumor's blood supply and oxygenation, making it more vulnerable to radiation therapy."

Although some animal studies have suggested that combining antiangiogenesis and radiation therapy can slow tumor growth, in others the treatment appeared to spur tumor growth. The current investigation was designed to resolve these conflicting results and to improve understanding of the cellular and molecular underpinnings of antiangiogenesis treatment. The MGH researchers implanted human brain tumor tissue into mice that were then treated with various combinations of an angiogenesis inhibitor called DC101 and radiation therapy.

DC101 alone produced a minor delay in tumor growth, and radiation alone produced a more significant growth delay. But of five different schedules of combined treatment, o
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
20-Dec-2004


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