Research: Bioengineered protein may stop cancer metastasis

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 blood stream 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 blood
stream and prevents them from linking with
and activating the Axls present on cancer
cells.
In collaboration with Professor Amato
Giaccia, who heads the Radiation Biology
Program in Stanford's 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 non-toxic in
pre-clinical experiments," Giaccia said. "It
could open up a new approach to cancer
treatment."
Giaccia and Cochran are scientific advisors
to Ruga Corp., a biotech startup in Palo
Alto that has licensed this technology from
Stanford. Further preclinical and animal
tests must be done before determining
whether this therapy is safe and effective in
humans.
Greg Lemke, of the Molecular Neurobiology
Laboratory at the Salk Institute, called this
"a prime example of what bioengineering
can do" to open up new therapeutic
approaches to treat metastatic cancer.
"One of the remarkable things about this
work is the binding affinity of the decoy
protein," said Lemke, a noted authority on
Axl and Gas6 who was not part of the
Stanford experiments.
"The decoy attaches to Gas6 up to a
hundredfold more effectively than the
natural Axl," Lemke said. "It really sops up
Gas6 and takes it out of action."

Source:
Stanford School of Engineering