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Combo of Avastin, second drug shows promise fighting brain cancer, Mayo Clinic finds
Date:2/14/2013

nk"href="http://www.mayoclinic.org/rochester/">Minnesota.

The research began after Dr. Anastasiadis, a basic scientist who studies cell adhesion and migration, gave a seminar to a group of oncologists who treat brain tumors. The issue of bevacizumab-induced invasion was brought up and a collaboration to study it was quickly set up and funded by the Mayo Clinic Specialized Program of Research Excellence (SPORE) grant for brain cancer, one of only four in the country.

The issue of bevacizumab's induced aggressiveness is not limited to brain cancer, Dr. Anastasiadis says.

"While Avastin offers clear benefit in some patients, oncologists have noted that when cancers of many types recur after use of Avastin, they become aggressive and invasive," he says.

The team discovered that as brain tumors become more aggressive after use of bevacizumab in mice, the cancers begin inducing a family of kinases known as Src, which then activate proteins found at the edge of brain tumors. These proteins essentially give the tumor cells "legs" upon which to crawl away and find a new source of nutrition, Dr. Anastasiadis says.

"Anti-angiogenesis drugs like Avastin deprive tumor cells of blood nutrients, so the tumors shrink initially, but we believe that this deprivation acts like a switch to turn on proteins that help the cancer cells migrate to other parts of the brain in search of blood," he says. "In short, if Avastin does not allow a tumor to make new blood vessels to feed it, the tumor will move to other existing blood vessels."

The researchers then tested dasatinib, a drug that inhibits Src kinases. They found that while use of bevacizumab or dasatinib alone did not provide much benefit in mouse models of human glioblastoma, use of both together shrank tumors and blocked any subsequent spread.

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Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-2299
Mayo Clinic
Source:Eurekalert

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