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Clinical studies in the pipeline: the therapies of tomorrow in trials today
Date:10/23/2007

rm study so there is need for more research to confirm this potential benefit, and to examine safety more closely. The treatment was generally well tolerated in most patients, Dr. Zhu says, but adds that grade three and four toxicities were observed in approximately three to 20 percent of patients, depending on the specific side effect.

HCC is most commonly found in patients with chronic viral hepatitis (B or C) or with cirrhosis, and surgery to remove tumors is only possible in a small percentage of patients. Generally, patients have a poor prognosis because these tumors produce a lot of proteins, such as VEGF and VEGFR2, that make them highly vascular and able to build a solid and nurturing blood supply with increased ability to invade surrounding major vessels and to metastasize, Dr. Zhu says. Sunitinib is a receptor tyrosine kinase inhibitor designed to target and block VEGFR2 activity, among other pro-growth molecules.

To find out if sunitinib could target HCC, the research team employed a number of research tools to measure changes in the patients blood and tumor perfusion. Instead of just trying to determine if the drug is attacking the tumor, we want to get a sense of what kind of changes the agent might be inducing, Dr. Zhu said. We want to know what the mechanisms are that might confer benefit as well as toxicity.

The team used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess changes in the permeability of tumor blood vessels and found that it decreased by an average of 38 percent after two weeks of sunitinib therapy. Using protein arrays to test for angiogenic biomarkers in the blood, the investigators found that the levels of VEGF and PIGF increased, while that of soluble VEGFR2 declined in most patients. Also, flow cytometry analyses of blood cells suggested that circulating endothelial cells increased in some patients while circulating progenitor cells were significantly decreased, indicating that sun
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Contact: Greg Lester
greg.lester@aacr.org
267-646-0554
American Association for Cancer Research
Source:Eurekalert

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