Combo of Avastin, second drug shows promise fighting brain cancer, study finds

February 14, 2013

The drug bevacizumab, also known by the trade name Avastin, shrinks tumors briefly in patients with an aggressive brain cancer known as glioblastoma multiforme, but then they often grow again and spread throughout the brain for reasons no one previously has understood. Now, Mayo Clinic researchers have found out why this happens. They have also discovered that pairing Avastin with another cancer drug, dasatinib, can stop that lethal spread. Dasatinib is approved for use in several blood cancers.

The findings, based on an animal study, are detailed in the Feb. 14 online issue of . Based on those results, Mayo Clinic has already conducted a phase I clinical trial testing a combination of and dasatinib in glioblastoma patients whose other therapies failed. Mayo is now carrying out a randomized phase II study of 100 patients through Alliance for Clinical Trials in Oncology, a clinical trials network supported by the National Cancer Institute.

"We are very encouraged. This finding could potentially benefit many ," says co-author Panos Z. Anastasiadis, Ph.D., chair of the Department of at Mayo Clinic in Florida. Working with him were researchers and oncologists from Mayo Clinic campuses in Florida and 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 . 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 , 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 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.

"If you block that migration, the cells are forced to stick together and hopefully die by lack of nutrition," Dr. Anastasiadis says.

Researchers next will work to identify which patients benefit the most from this new treatment, which do not, and why.

Explore further: Better treatment for brain cancer revealed by new molecular insights

Related Stories

Better treatment for brain cancer revealed by new molecular insights

July 9, 2012
Nearly a third of adults with the most common type of brain cancer develop recurrent, invasive tumors after being treated with a drug called bevacizumab. The molecular underpinnings behind these detrimental effects have now ...

Avastin, Sutent increase breast cancer stem cells, study shows

January 25, 2012
Cancer treatments designed to block the growth of blood vessels were found to increase the number of cancer stem cells in breast tumors in mice, suggesting a possible explanation for why these drugs don't lead to longer survival, ...

Study unravels biological pathway that controls the leakiness of blood vessels

December 17, 2012
(Medical Xpress)—A research team led by scientists at Mayo Clinic in Florida have decoded the entire pathway that regulates leakiness of blood vessels—a condition that promotes a wide number of disorders, such as heart ...

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.