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Swallow a gene to treat and
prevent cancer? May be possible
26 FEBRUARY 2001-- In a stunning result in
laboratory mice, researchers, have for the first time devised
a technique to prevent cancer using a therapeutic gene delivered
orally.
A team of cancer geneticists and neuroscientists
led by Dr. Carlo Croce, director of the Kimmel Cancer Center
in Philadelphia, greatly reduced the incidence of stomach cancer
in mice bred to be genetically prone to develop tumors, and had
been exposed to a cancer-causing substance.
"This is the first time we can prevent
cancer by using gene therapy," says Croce in a prepared
statement. "The technique could have potential use in several
human conditions, such as in precancerous lesions in the lung,
esophagus, head and neck, bladder and cervix."
While it's too early to say how effective
this may be in humans, the work is another step in the development
of safe and effective use of gene therapy for cancer.
Croce and colleagues Drs. Kay Huebner, Matthew
During, at Jefferson Medical College and their co-workers report
their results in today's online version of the Proceedings
of the National Academy of Sciences. The article will appear
in the printed journal March 13.
"We were pretty surprised that it worked
so well," said Huebner in a prepared statement. "We
knew we could kill cancer cells in the laboratory, but we didn't
know if the viruses would get eaten up by the stomach juices.
We expected differences, but not so dramatic."
In the study, the researchers created 12 genetically
altered "knockout" mice, so named because they lack
a gene called FHIT, which is normally located on chromosome 3.
When damaged, FHIT has already been implicated in contributing
to a number of cancers, such as esophageal, stomach, kidney,
breast and lung.
Each mouse was exposed to nitrosomethylbenzylamine
(NMBA), a carcinogen, beginning four weeks prior to therapy.
The scientists' plan was to cause tumors to develop and then
try to either prevent or slow their growth with gene therapy.
All of the 12 control mice receiving NMBA
developed tumors. Each of eight mice in three therapy groups
received one dose of gene therapy with a different type or combination
of viral delivery systems. The viruses used are genetically engineered
to carry the therapeutic gene into the cell nucleus.
The results clearly showed a difference in
the number of tumors. Among the untreated mice, all developed
several tumors in the stomach. In the mice treated with adeno-FHIT,
50 percent had tumors. In the AAV mice, only three of eight had
tumors. As a result, the researchers believe the AAV delivery
method might result in longer expression of the FHIT gene.
"These results are very exciting,"
During says. "This is one of the first studies to demonstrate
a gene transfer that is prophylactic. On the heels of the recent
announcement of the sequencing of the human genome and our growing
ability in genetic profiling, it's a step toward enabling us
to treat high-risk individuals and reduce the likelihood of cancer."
The scientists think the technique may be
a novel early stage approach to prevent and perhaps treat cancer.
The scientists say many hurdles still remain
to effective and widespread use of gene therapy for cancer, not
the least of which is getting the virus into every cell affected.
Many regard gene therapy not so much a potential cure but another
weapon in the array of treatments aimed at controlling cancer.
Huebner says, the approach needs a lot more
study, adding that scientists would have to develop different
techniques to deliver genes to other areas of the body, such
as the lung, kidney and liver.
One next step for the research team is to
develop other animal tumor models with FHIT gene knockouts for
both cervical and lung cancer.
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