Taking Bulls-eye Aim Against Two Cancer Targets

Cancer caves when cMET and VEGF are targeted simultaneously

(RxWiki News) The capacity of cancer to outsmart its opponents is legendary. That's why therapies have to be multifaceted. New research shows that going after two targets hits the bulls-eye in knocking the lights out of tumors.

Targeting two molecules - c-MET and vascular endothelial cell growth factor (VEGF) - was shown to annihilate tumors, making them powerless to spread in mice.

This finding may result in improving the effectiveness of combination therapies and have broad application in treating a number of cancers.

"Ask your doctor about combination therapies."

Scientists at the University of California, San Francisco (UCSF) conducted the study to test the two-pronged attack. Donald McDonald, M.D., Ph.D. led the research. He is a member of the UCSF Helen Diller Comprehensive Cancer Center and the Cardiovascular Research Institute and a professor of anatomy.

"It's the combination of approaches—there's a synergy between the two," Dr. McDonald said. "You add two and two, and you get 10."

Researchers worked with mice that had a rare form of cancer known as neuroendocrine pancreatic tumors.

The drugs used in the experiments are either already on the market or currently being tested in clinical trials. 

What the scientists were targeting are two proteins that both play key roles in malignant tumors:

  • c-MET is a marker that indicates how aggressive a cancer is; it's also involved in cancer invasion and metastasis.
  • VEGF assists tumors grow their own blood supply that feeds and helps the cancers grow.
  • Drugs that target VEGF block the tumor's blood supply.

Drugs that target these molecules are currently on the market. Avastin was approved by the U.S. Food & Drug Administration (FDA) in 2004 to treat advanced colon cancer. It was approved in 2008 to treat metastatic breast cancer, but that approval has since been revoked.

Previous research has found that Avastin-like drugs not only shrink tumors, but also transformed the tumors from roundish balls into oddly shaped masses with tendrils that invaded surrounding tissues and other organs. This work suggested that the VEGF wall makes tumors more aggressive. 

So in this work, Dr. McDonald and his colleagues found that blocking both VEGF and c-MET in mice is more effective than blocking either alone. The one-two punch not only slows tumor growth but also stymies invasion and metastasis.

This approach morphed aggressive tumors with invading fingers and many metastases into tiny balls with few or no metastases.

Researchers worked with several drugs in this study. Cabozantinib targets both molecules. Other drug combinations can also be used to block the molecules at play.

More testing is needed to confirm the safety and effectiveness of this two-target approach, according to Dr. McDonald. And it may be a year or more before these drugs are available to patients, he said.

Clinical trials are currently being conducted to test the effectiveness of this approach in humans who have prostate cancer, breast cancer, and other types of cancer. 

Results of this study were published February 24, 2012 in the journal Cancer Discovery.

This study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute. Additional support was provided by the companies Pfizer and Exelixis and by AngelWorks Foundation.

None of the UCSF authors has any financial interest in the companies that manufacture the drugs used in the experiments, which also involved scientists at Pfizer and Exelixis.

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Review Date: 
March 1, 2012