Proteomics Shows Promise in Colon Cancer Chemoprevention Study
Using new technology associated with the study of proteins, or
proteomics, scientists at the National Cancer Institute (NCI), part
of the National Institutes of Health (NIH), and their colleagues
have made a step toward predicting which people with familial adenomatous
polyposis (FAP), an inherited condition that often leads to colon
cancer, will respond to the prevention drug celecoxib. This study,
published in the April 15, 2004, issue of the journal Cancer Research,
is the first to report using proteomics techniques to find a possible
predictor of response in a chemoprevention trial.
Iqbal U. Ali, Ph.D., in the NCI Division of Cancer Prevention, and
collaborators examined protein patterns among people who had been
given celecoxib in a chemoprevention clinical trial in which the
drug reduced the number of colon polyps characteristic of patients
with FAP. Celecoxib inhibits an enzyme called cyclooxygenase 2,
which has been associated with various cancers in addition to colon
cancer. These clinical trial results were reported in
June 2000 and led to approval by the Food and Drug Administration
of celecoxib as a chemoprevention agent for people with FAP.
Not everyone in the 2000 study taking celecoxib experienced polyp
reduction, however. Ali's group, employing a new proteomics technique,
was able to distinguish the people who responded to the drug from
those who did not.
Ali's laboratory used serum from the blood of 55 people who had
participated in the celecoxib prevention trial. Serum contains tens
of thousands of proteins. Using a specialized form of mass spectroscopy
as a proteomics tool, the patients' proteins were separated and
reported as a series of peaks. The pattern of protein peaks can
be used to differentiate groups of patients.
The scientists analyzed blood obtained at the beginning of the prevention
study before participants received any celecoxib and compared
the pattern of protein peaks from the patients who didn't respond
to the drug to the protein pattern of those who had a good response.
One particular protein peak occurred in the serum of those people
who did not benefit from the drug. The same protein peak was absent
in those people whose polyps were reduced.
Although the technique has not been tested enough to be used in
the clinic to identify those with FAP who will respond to celecoxib,
the scientists are refining the technique for possible future clinical
"This study is a promising first step in using proteomics for
personalized colon cancer prevention," said Ali. "A lot
more work is needed before patients' responses to specific chemopreventive
drugs can be reliably predicted."
In addition to predicting who responded to celecoxib, the scientists
also used the proteomics technique to look at how protein patterns
in each patient changed after being given the drug. They found that
of thousands of possible proteins, only a few protein peaks were
changed significantly in all patients following administration of
celecoxib. The researchers are now trying to identify these proteins
to learn more about how the drug works.
For information about cancer, please visit the NCI home page at
http://cancer.gov or call NCI's
Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Questions and Answers: Proteomics and Cancer: http://www.nci.nih.gov/newscenter/pressreleases/proteomicsQandA.