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    Warning Sign for Cancer Drugs

    Drugs That Block Tumor Blood Vessels May Harm Normal Cells

    VEGF Inside Cells continued...

    "We found this survival signal is occurring inside of the cells," Iruela-Arispe says. "It makes perfect biological sense. The cell needs to respond quickly -- it doesn't have time to say, 'Where is the VEGF?'"

    Avastin only affects the VEGF receptors, or switches, on the outside of cells. This means it may not be as potentially harmful as drugs that block the VEGF switches on the inside of cells, Iruela-Arispe says.

    "This may be the reason we don't see more frequent dangerous side effects from Avastin," she says. "But about 5% of Avastin patients have blood clots, and many have high blood pressure that we don't yet understand. Newer, smarter drugs go inside the cell and focus on the inside pool of VEGF receptors as well as the outside pool. These will have more side effects than Avastin does."

    None of this means cancer patients should avoid VEGF inhibitors.

    "If I had an aggressive cancer, I would take these drugs -- even the new ones," Iruela-Arispe says. "If my choice is dying from cancer in six months or taking a risk of a side effect that may never happen, I will certainly take the risk. These are great drugs, but we should continue the search for better ones."

    Francis says the message is not that VEGF inhibitors are bad, but that doctors and patients should be aware of the risks.

    "If you get into treatments targeting this VEGF pathway, it is going to have to be very carefully done," he says.

    Iruela-Arispe and colleagues report their findings in the Aug. 24 issue of the journal Cell.

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