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Setting a trap

The arrival of Avastin has affirmed the notion that antiangiogenic agents have a role in cancer treatment, researchers say. A so-called VEGF "sink," Avastin works by soaking up the growth factor released by tumors so they can't tap into the body's bloodstream.

Two other agents, dubbed SU-011248 and Bay43-9006, are in the latter stages of testing and represent a potential improvement over Avastin, which thus far has worked only in combination with standard chemotherapy. These drugs, which in some cases have single-handedly caused advanced kidney tumors to retreat, target two key proteins in the process by which tumors pipe in new blood.

Labs and pharmaceutical companies worldwide are creating and testing compounds to see if they have potential as antiangiogenic agents. The first batch of blood vessels to grow toward a tumor tend, like a cheap garden hose, to be full of leaks, making it difficult for some conventional chemotherapy drugs to reach the tumor. Angiogenesis inhibitors, by contrast, do not have to leave blood vessels to be effective; their ultimate target, after all, is the vessels themselves.

"We may discover that drugs targeting several aspects of the angiogenesis cascade — the series of events involved in bringing blood flow to tumors — offer the best approach," says Eder, clinical director of Phase I drug trials at DFCI. "The goal is that even if we can't eradicate tumors with chemotherapy or radiation, we can limit them to a size where they won't cause problems."

Eder and his Dana-Farber colleagues are leading and collaborating on a series of clinical trials of potential antiangiogenic therapies. Their aim is to learn whether such agents work, of course, but also to determine which types of cancer are most vulnerable to the treatment and in what doses, what stages of cancer respond best, and whether the drugs are effective alone or combined with other treatments.

Spring / Summer 2005, Paths of Progress

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Bringing blood vessels to light

One of the chief puzzles facing antiangiogenesis researchers is how to determine if potential therapies are effective. In the Stop & Shop Family Pediatric Brain Tumor Clinic at Dana-Farber, clinic director Mark Kieran, MD, is working on what might be called a "shining" possibility.

Using animal models developed in his laboratory, Kieran and his colleagues are exploring ways to make blood vessels in tumors light up on standard imaging scans. If successful, the technique would enable doctors to determine whether vessels continue to grow or are held in check by treatment with angiogenic agents.

A recent grant from the Children's Brain Tumor Foundation has given added momentum to this effort. "This grant will allow my colleagues and me to refine treatments that improve quality of life and enhance the tools available for tracking drug effectiveness," Kieran states. "The benefits to children around the world could be very significant."