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Researchers Find Drug that Blocks Spread of Lung
Cancer in Mice
Possible progress against leading cause of cancer
deaths
Sept. 9, 2005 - Researchers at UT Southwestern
Medical Center have found a compound that shows promise as a way to
block the spread, or metastasis, of lung cancer. The compound blocks an
enzyme that is known to keep cells immortal and that is implicated in
almost all human cancers.
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Dr. Shalmica Jackson, postdoctoral
researcher in cell biology, and Dr. Jerry Shay and Dr. Woodring
Wright, professors of cell biology, have found that an
experimental drug effectively blocks the spread of human lung
cancer in mice. |
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July 6, 2005 - A major study that includes nearly
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The authors did conclude that a beneficial effect on lung cancer cannot
be ruled out. Read more...
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From results in test on mice, they determined that
the compound, called GRN163L, also works rapidly and in doses that would
be reasonable for therapy. It may be particularly useful after surgery
or in combination with chemotherapy or radiotherapy to prevent residual
cancer cells from spreading.
"We showed for the first time that this drug can
work in animals," said
Dr. Jerry Shay, professor of cell biology at UT Southwestern and
senior author of the study, which appears in the September issue of the
journal Cancer Research.
Lung cancer is the leading cause of cancer death,
killing more people than breast cancer, prostate cancer and colon cancer
combined, according to the American Cancer Society.
Lung adenocarcinoma accounts for about 40 percent
of lung cancers. Its rate is increasing worldwide, Dr. Shay said, and
survival rates are poor because the disease metastasizes, usually by the
time treatment begins in most cases.
The researchers designed, synthesized and tested
GRN163L, which consists of 13 nucleotides, the units that make up DNA,
plus a fatty section that improves the rate at which cells take it in.
GRN163L specifically matches a stretch of DNA at
the end of the chromosome, a segment called the telomere. Normally, as
cells divide and age, telomeres become shorter and shorter. When they
reach a certain length, the cells stop dividing.
But the telomeres in cancerous cells stay the same
length, thanks to an enzyme called telomerase. The gene that creates
telomerase is active in about 85 percent to 90 percent of tumors and in
only a few noncancerous cells.
"Telomerase is the immortalizing gene," said Dr.
Shay.
Telomerase doesn't cause cancer, but it allows the
cancer cells to keep dividing. It's almost a universal target for
fighting cancer, Dr. Shay said, and its specificity is what makes it
attractive for attack. Telomerase works by binding to DNA and, with a
protein section, keeping the chromosome from getting shorter. GRN163L
apparently prevents telomerase from binding.
The researchers injected human lung tumor cells
into the tails of mice and found that GRN163L blocked the development of
metastatic tumors over several months. The higher the dose, the fewer
tumors there were.
"That suggests that this drug prevented the lung
metastasis," Dr. Shay said, noting that the reactions took place at
doses that would be considered reasonable for treatment. The compound
might not be effective, however, in someone in whom metastasis has
already begun, he said.
The research was partly responsible for getting the
drug into clinical trials, where it will soon be tested on humans, Dr.
Shay said. The trials, recently approved by the Food and Drug
Administration, are at an early stage, in which the drug is simply being
tested for safety.
"We will be surprised if we see any toxicity," he
said.
Future experiments on animals will involve
combining GRN163L with other drugs and with radiation and therapy to see
how it interacts with these other cancer treatments.
"What we're really interested in is getting this
novel therapeutic to work, to minimize the suffering and pain that
people have with cancer therapy," Dr. Shay said.
Other UT Southwestern researchers involved in the
study were Drs. Gunnur Dikmen and Ginelle Gellert, former postdoctoral
researchers in cell biology, Dr. Shalmica Jackson, postdoctoral
researcher in cell biology, and Dr.
Woodring Wright, professor of cell biology. Researchers from the
Geron Corp. also participated.
The work was supported in part by the National
Cancer Institute, Geron Corp., Tubitak and the Turkey Education
Foundation in Turkey.
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