So Weichselbaum's team compared the anti-tumor effects of anti-VEGF alone, radiation alone and the two in combination on mice with several different types of cancer.

In all four tumor types studied -- Lewis lung carcinoma, human squamous cell carcinoma, human esophageal adenocarcinoma and a glioblastoma -- the combined therapy was much more effective than either anti-VEGF or radiation therapy alone.

"The antitumor effects were greater than additive," note the authors. "Even a slight inhibition of VEGF action can result in a marked increase in the antitumor effect of ionizing radiation."

For example, giving mice with Lewis lung carcinoma a small dose of anti-VEGF reduced tumor size by 42.6 percent. Treatment with low doses of radiation alone reduced tumor size by 43 percent. But treatment with low doses of anti-VEGF and radiation resulted in reduction of tumor size by 78 percent.

Combined treatment also slowed re-growth of these rapidly expanding tumors. It took untreated Lewis lung carcinoma tumors only 2.6 days to double their original volume. Tumors treated with anti-VEGF required 3.4 days. Tumors treated with radiation therapy took four days, but those treated with radiation and anti-VEGF took nine days.

To uncover how the combination altered tumor growth, the researchers exposed human tumor cells and blood vessel cells in the test tube to VEGF, anti-VEGF and radiation. Neither VEGF nor anti-VEGF affected tumor cells, but adding VEGF protected blood vessel cells from radiation and adding anti-VEGF made blood vessel cells more susceptible to radiation.

"The combination of anti-VEGF and radiation therapy was much more effective than we might have expected," said Weichselbaum. Removing VEGF "not only slowed tumor recovery from treatment, it actually appeared to make existing tumor blood vessels more suscept
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Contact: John Easton
jeaston@mcis.bsd.uchicago.edu
773-702-6241
University of Chicago Medical Center
15-Jul-1999