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Giving cancer the cold shoulder
By Rachele Kanigel
In the 1840s a British physician named James Arnott used a solution
of crushed ice and sodium chloride to freeze cancers in the breast
and uterus. Ever since these primitive experiments, doctors have
been trying to harness the power of freezing to kill cancer, and
advances in the past 20 years have catapulted cryosurgery into
the mainstream of cancer therapy.
But despite its growing use in the treatment of skin, breast,
liver, kidney, and prostate cancer, cryosurgery has its limitations,
says Boris Rubinsky, a Berkeley professor of bioengineering and
mechanical engineering who helped pioneer modern techniques in
cryosurgery. Now Rubinsky is exploring a tantalizing new strategy:
cryochemotherapy. By combining freezing with chemotherapy, he
and his colleagues hope to more precisely target malignant cells,
while sparing healthy tissue around them. Cryosurgery is performed
by inserting one or more cryoprobes, thin needles cooled with
either argon gas or liquid nitrogen, into a tumor, turning the
malignant mass into an ice ball. Doctors see where they are operating
and monitor the freezing using ultrasound or magnetic resonance
imaging, employing techniques developed by Rubinsky and radiologist
Gary Onik in the 1980s and ’90s.
 |
| Graduate
student Jessica Preciado works with Rubinsky in the Bio-Thermal
Engineering Lab, conducting tests on cancer cells frozen at
various rates and temperature gradients to determine which
combination works best to kill the maximum number of cells.
Photo: Peg Skorpinski |
"The problem is that freezing does not necessarily destroy
the tissue," explains Rubinsky. "At the heart of the
frozen lesion, the cells will be destroyed, but on the edge, the
outer rim, some of the cells will survive." As a result,
doctors typically freeze an area well beyond the tumor. But this
overshooting can cause significant complications. In the treatment
of prostate cancer, for example, freezing healthy cells around
the cancerous lesion can damage the nerves, leading to impotence.
"You don’t want to destroy what you don’t have
to," Rubinsky says.
The first experiments on cryochemotherapy, conducted with scientists
from the Institut Gustave-Roussy in Villejuif, France, have been
promising. Last May, Rubinsky and Luis M. Mir, a senior researcher
at the French institute, reported in the British Journal of Cancer
that freezing cancer cells in test tubes made them far more vulnerable
to attack by bleomycin, a potent anti-cancer drug.
In the study, researchers froze melanoma cells at about -14 degrees
Celsius, a temperature at which cells on the outer rim of a frozen
lesion often survive cryosurgery. The cells were then treated
with trace amounts of bleomycin, which is toxic to cancer cells
but can be ineffective because it has difficulty penetrating cells.
What the researchers learned was that freezing helped the bleomycin
enter the cells. Even tiny amounts of the toxic chemical, several
magnitudes smaller than what is typically used in patients, killed
most of the cancer cells.
Rubinsky hopes that by combining the two therapies scientists
can create a regimen that’s more effective and less debilitating
than either strategy used alone. "When you add chemotherapy
to cryosurgery you have a minimally invasive technique that has
the precision of a scalpel," he says. The next step is to
find the best way to administer bleomycin or other chemotherapy
agents to the cancerous cells, says Onik, Rubinsky’s longtime
collaborator on cryosurgery research. "We don’t know
whether it’s better to inject the bleomycin intravenously
or to inject it directly into the cancer," says Onik, now
director of surgical imaging at Celebration Health, a treatment
center in Orlando, Florida. "Certain details still have to
be worked out."
Onik, one of the world’s leading cryosurgeons, says marrying
these two techniques could also alter the way cryosurgery is performed.
Often the procedure involves a cycle of treatments in which tumors
are frozen, allowed to thaw, then frozen again. With cryochemotherapy,
physicians might only have to freeze the tumor once.
Dr. Israel Barken, a urologic oncologist in San Diego and chairman
of the Prostate Cancer Research and Education Foundation, is also
excited about the combination treatment, particularly for the
treatment of prostate cancer.
Cancer of the prostate presents a difficult challenge for physicians
because of the danger of damaging vital structures like the urethra
and the nerves that control erection. About 90 percent of prostate
cancer patients who undergo aggressive cryosurgery suffer impotence,
and five to ten percent experience incontinence, Barken says.
With cryochemotherapy, cryosurgeons may be able to take a less
aggressive stance, dramatically reducing the debilitating complications.
"The beauty of this approach is the synergistic effect of
pairing cryosurgery with chemotherapy," says Barken. "By
using bleomycin, there’s no need to be as aggressive with
the cryosurgery. By freezing the cells you can use very low doses
of bleomycin. This should drastically reduce the harmful side
effects of using either treatment alone."
New treatments typically take years to go from lab bench to the
bedside. But because cryochemotherapy involves two federally approved
treatments, Rubinsky says, it may be ready for clinical use in
a matter of months. "I think before too long chemotherapy
will be used in conjunction with all cryosurgery," says Rubinsky.
Rubinsky, whose research in such diverse fields as tissue engineering,
cryopreservation, and biomedical instrumentation have led colleagues
to call him "the Thomas Edison of bioengineering," says
it’s been satisfying to watch cryosurgery go from a little-used
technique in the early 1980s to a life-saving operation performed
on tens of thousands of cancer patients. When he started his line
of research, cryosurgery was primarily limited to the treatment
of skin cancer because physicians needed to see what they were
doing. It wasn’t until he and Onik linked cryo-surgery with
ultrasound monitoring that surgeons could confidently use the
technique inside the body.
In the mid-1990s, Rubinsky and Onik demonstrated that magnetic
resonance imaging, which provides three-dimensional pictures of
tissue and tumors, could further expand the limits of cryosurgery.
With this new advance combining freezing with chemotherapy, Rubinsky
hopes to push cryosurgery further into the mainstream of cancer
treatment. "This will make cryosurgery more precise and more
effective," he says.
Author Rachele Kanigel is an assistant professor
of journalism and media analysis at California State University
Monterey Bay. She also writes about medicine for Time, Health,
Reader's Digest, and other publications. |
