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Cancer drugs my build and not tear down blood vessels
Date:11/9/2008

Scientists have thought that one way to foil a tumor from generating blood vessels to feed its growth a process called angiogenesis was by creating drugs aimed at stopping a key vessel growth-promoting protein. But now the opposite seems to be true.

Researchers at the Moores Cancer Center at the University of California, San Diego (UCSD) in La Jolla have found evidence that blocking that protein target, called VEGF, or vascular endothelial growth factor, doesn't really halt the process at all. Instead, cutting levels of VEGF in a tumor actually props up existing blood vessels, making them stronger and more normal, and in some cases the tumors larger. But as a result, the tumor is more vulnerable to the effects of chemotherapy drugs.

In a paper appearing online November 9, 2008 in the journal Nature, David Cheresh, Ph.D., professor and vice chair of pathology at the UC San Diego School of Medicine and the Moores UCSD Cancer Center and his co-workers mimicked the action of anti-angiogenesis drugs by genetically reducing VEGF levels in mouse tumors and inflammatory cells in various cancers, including pancreatic cancer. They also used drugs to inhibit VEGF receptor activity. In every case, blood vessels were made normal again.

The researchers say the findings provide an explanation for recent evidence showing that anti-angiogenesis drugs such as Avastin can be much more effective when combined with chemotherapy. The results may lead to better treatment strategies for a variety of cancers.

"We've discovered that when anti-angiogenesis drugs are used to lower the level of VEGF within a tumor, it's not so much a reduction in the endothelial cells and losing blood vessels as it is an activation of the tumor blood vessels supporting cells," said Cheresh. "This enables vessels to mature, providing a conduit for better drug delivery to the tumor. While the tumors initially get larger, they are significantly more sensitive
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Contact: Steve Benowitz
sbenowitz@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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