March 5, 2004
Stalking a stealthy disease: Hunting early warning signs in ovarian cancer
Technology of today
Large-scale searching for biomarkers in blood or urine depends on techniques used in proteomics, a field devoted to cataloguing the tens of thousands of proteins in cells and discovering their functions. The main tool is a mass spectrometer, which sorts out the proteins in a biological sample and ranks them by size and amount. It is hoped that ovarian cancers will be distinguished by a distinctive pattern of proteins — a "fingerprint" that can allow diagnoses in early stages of the disease. Advances in the past 10 years even enable scientists to identify the specific proteins responsible for the patterns, using a process called protein sequencing, which may take many weeks.
Dr. Cramer and colleagues have recently identified two promising marker candidates — alpha chain haptoglobin and eosinophil-derived neurotoxin. "Prior to this, only a handful of biomarkers were discovered over the last 10 years and only one or two were viable," says Sam Mok, MD, director of the Laboratory of Gynecologic Oncology at Brigham and Women's. "With the new proteomics and genomic technology that we're now using, we have identified many more marker candidates in just two years time."
Because it is difficult to find any single protein in a cell, serum, or urine that will show itself 100 percent of the time, multiple markers are more sensitive as a screening tool. The challenge now, adds Dr. Mok, who is also on the faculty at Dana-Farber, is to select individual biomarkers and combine them into sets, while continuing to seek out new markers.
"We would like to know which markers will work best when used together in a panel of, say, five markers — not too many," he explains. "These will be chosen using biostatistical models and software. Each marker will complement the other. For example, a group of markers with 80 percent sensitivity would be tested using serum and urine from healthy women compared to samples of women with ovarian cancer. If one doesn't work, we'll add another combination and study it again until we find a panel that's 100 percent effective."
The investigators estimate that it will be at least five years before they will have panels of markers that reliably predict ovarian cancer. However, once the best model has been established, it must be verified in tests on a larger population of women. Then it will have to go through the U.S. Food and Drug Administration approval process, which generally takes one or two years.
Nevertheless, Dr. Cramer remains optimistic: "As the National Cancer Institute and the Early Detection Research Network have made this a primary mission, I believe we can expect to see new markers for not only ovarian cancer, but a variety of cancers, within the next five years."
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