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A genetic 'gang of 4' drives spread of breast cancer

apillaries, they just got stuck there," said Massagué. "We concluded that metastatic cells use these same genes to loosen up cells in capillaries, so that the cells can penetrate the lung tissue to grow there.

"These findings provide a beautiful explanation for how the genes that we identified in breast cancer patients as being associated with lung metastasis manipulate blood vessels to give them an advantage both in the primary tumors and in the lung," he said.

Two drugs already on the market act directly on proteins produced by the genes Massagué’s group had been studying. Cetuximab is an antibody that blocks the action of epiregulin and is used to treat advanced colorectal cancer. Celecoxib is an inhibitor of COX2 that is used as an anti-inflammatory, and is being tested in clinical trials against many types of cancer. The researchers also tested whether cetuximab and celecoxib would work effectively in concert to reduce metastasis in mice.

"We found that the combination of these two inhibitory drugs was effective, even though the drugs individually were not very effective," said Massagué. "This really nailed the case that if we can inactivate these genes in concert, it will affect metastasis," he said.

Massagué said that while clinical trials of the drug combination are being discussed, "there are already treatments to diminish the chance of metastasis in breast cancer, so such trials would have to be designed very carefully to understand how and whether the new drug combination would be of additional benefit." In the article published in the Proceedings of the National Academy of Sciences, Massagué and his colleagues explored how the entire group of 18 genes, called the ‘lung metastasis gene-expression signature?(LMS) influenced both breast tumor growth and spread to the lungs. Co-authors on the paper were from the University of Chicago, The Netherlands Cancer Institute, Veridex L.L.C., The Cleveland Clinic and the Erasmus Me
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Source:Howard Hughes Medical Institute


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