By: Stephanie M. Lee
From: sfgate.com
Most cancer patients don’t die because of a single tumor, but rather multiple tumors that spread throughout the body.
A new therapy, developed by Stanford University researchers and licensed by a local biotech startup, appears to disrupt the deadly process known as metastasis, which causes cancer cells to break away from the original tumor sites and grow elsewhere.
So far, the protein therapy has only been tested in mice, and it would take years to clear the required clinical trials in other animals and then humans. But researchers say the treatment, described in a study published online this week in the journal Nature Chemical Biology, could be a promising way to someday slow or stop the spread of aggressive tumors without chemotherapy.
“Most patients, when they come in at an advanced-disease stage, have metastatic disease and there are no real drugs out there that can help them,” said Ray Tabibiazar, CEO of Ruga Corp., the privately held San Francisco cancer-drug developer that has licensed the Stanford team’s technology. “This is probably one of the first drugs that seems to be targeting that specific process.”
Cancer therapies designed to target the genetics of specific tumors are helping to fuel the $91 billion global cancer-drug market, which will grow 5 percent annually, according to the IMS Institute for Healthcare Informatics.
To stop cancer from spreading, the Stanford team came up with a way to keep two proteins, Axl and Gas6, from interacting.
Axl proteins are “like a molecular antennae on the surface of cancer cells, waiting to receive signals from the environment,” said Jennifer Cochran, an associate professor of bioengineering at Stanford who oversaw the project. Gas6, on the other hand, is a molecule that travels through the bloodstream and binds to Axl.
When two copies of Gas6 link to two Axls, the process sends out biochemical signals that enable malignant cancer cells to leave the site and migrate to other parts of the body.
So the Stanford team, led by bioengineering graduate student Mihalis Kariolis, engineered a harmless version of Axl — a decoy that also binds with Gas6, but does not transmit the signals that allow the cancer cells to proliferate.
“The work is potentially quite interesting and significant,” said Greg Lemke of the Salk Institute for Biological Studies in La Jolla, who is an expert on the proteins used by the Stanford team but was not involved with the research. He commended the decoy Axl protein for its effective, “remarkably tight” bind to Gas6.
The scientists administered the intravenous therapy to mice with aggressive breast and ovarian cancers. A few weeks later, the mice who had received the breast-cancer treatment had 78 percent fewer metastatic sites than the untreated mice. And those who had received the ovarian-cancer treatment had 90 percent fewer metastatic sites compared to the control group.
“We were pretty excited and pretty stunned,” said Cochran, who was a senior author on the paper along with Amato Giaccia, head of the Radiation Biology Program in the Stanford Cancer Center. They are also both scientific advisers to Ruga.
Not only was the therapy effective and simple to administer, it resulted in no toxic side effects, the researchers said. Should it play out the same way in humans, doctors could use the therapy instead of chemotherapy, which, even when it works, can cause altered blood counts and nausea.
Tabibiazar, Ruga’s CEO, said the company is testing the technology in a broad range of cancers besides the ones studied by the Stanford team, including kidney, pancreatic and lung cancers.
But Lemke, the Salk expert, said Gas6 proteins are not equally important for all types of cancers to proliferate. The technology, like other new-generation targeted cancer drugs, may only be effective in a subset of tumors, he said.
In other words, the right levels of proteins must be present.
“What this paper shows is if that’s really occurring, this approach could be a really effective therapy,” Lemke said.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.