Stanford Researchers Create “Evolved” Protein that May Stop Cancer from Spreading

Jennifer Cochran and Amato Giaccia led a team of researchers who have developed an experimental therapy to treat metastatic cancer. (Photo: Rod Searcey)

Experimental therapy stopped the metastasis of breast and ovarian cancers in lab mice, pointing toward a safe and effective alternative to chemotherapy.

A team of Stanford researchers has developed a protein therapy that disrupts the process that causes cancer cells to break away from original tumor sites, travel through the bloodstream and start aggressive new growths elsewhere in the body.

This process, known as metastasis, can cause cancer to spread with deadly effect.

“The majority of patients who succumb to cancer fall prey to metastatic forms of the disease,” said Jennifer Cochran, an associate professor of bioengineering who describes a new therapeutic approach in Nature Chemical Biology.

Today doctors try to slow or stop metastasis with chemotherapy, but these treatments are unfortunately not very effective and have severe side effects.

The Stanford team seeks to stop metastasis, without side effects, by preventing two proteins – Axl and Gas6 – from interacting to initiate the spread of cancer.

Axl proteins stand like bristles on the surface of cancer cells, poised to receive biochemical signals from Gas6 proteins.

When two Gas6 proteins link with two Axls, the signals that are generated enable cancer cells to leave the original tumor site, migrate to other parts of the body and form new cancer nodules.

To stop this process Cochran used protein engineering to create a harmless version of Axl that acts like a decoy. This decoy Axl latches on to Gas6 proteins in the bloodstream and prevents them from linking with and activating the Axls present on cancer cells.

In collaboration with Professor Amato Giaccia, who leads the Radiation Biology Program in the Stanford Cancer Center, the researchers gave intravenous treatments of this bioengineered decoy protein to mice with aggressive breast and ovarian cancers.

Mice in the breast cancer treatment group had 78 percent fewer metastatic nodules than untreated mice. Mice with ovarian cancer had a 90 percent reduction in metastatic nodules when treated with the engineered decoy protein.

“This is a very promising therapy that appears to be effective and nontoxic in preclinical experiments,” Giaccia said. “It could open up a new approach to cancer treatment.”

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