|Genomes and Medicine
Diagnosing Ovarian Cancer by Proteomics
By Nancy Touchette
Less than two years after scientists reported a simple blood test that successfully detects ovarian cancer even in its early stages, clinical laboratories are gearing up to make the test available, possibly by year’s end. The test can detect an ovarian tumor while it is still small and potentially curable.
This most promising prospect for the detection of cancer in its earliest stages comes from the emerging field of clinical proteomicsthe study of patterns of proteins in human blood or other tissues.
Patients with ovarian cancer show few symptoms in the early stages of tumor growth, and by the time symptoms appear the disease has often progressed so far that the patient's survival chances are poor. More than 80 percent of ovarian cancer patients are diagnosed with late stage disease and only 35 percent of these patients survive for five years. In contrast, 95 percent of women survive if they are lucky enough to be diagnosed in the early stages.
In 2002, collaboration among scientists at the U.S. National Cancer Institute (NCI), the Food and Drug Administration (FDA), and Correlogic Systems, Inc., yielded a breakthrough in cancer diagnostics. The researchers reported in Lancet that a simple blood test correctly diagnosed ovarian cancer in a study of 116 women.
Proteomics offers significant hope for new diagnostic tests because it can be used to detect a pattern of proteins that are being produced by cancer cells anywhere in the body. These proteins are shed into the bloodstream and so can be picked up by the blood test. This is a great advantage because cancer can be detected without having to biopsy individual tissue samples.
“Proteomics offers real time, early detection, which until now has been an unmet medical need,” says Peter J. Levine, CEO of Correlogic. “A gene test offers a long-term forecast of disease risk. With a proteomic test it's more like looking out the window and saying ‘It's raining out now,’ than seeing a forecast for next week.”
In the original study, the researchers first developed a characteristic cancer profile by comparing patterns of proteins in the blood of healthy individuals to those of patients known to have ovarian cancer. They then used this information to identify which patients had ovarian cancer and which did not.
When the researchers analyzed the proteins in blood from 50 women with ovarian cancer and 66 healthy women, the test correctly identified all of the cases of ovarian cancer, including 18 patients with very early disease. The test correctly identified 63 out of 66 individuals with no disease and incorrectly indicated that three had cancer.
Since last year, the researchers have extended their study to more patients and report improved sensitivity and specificity of the diagnostic test. They have also used the technique to examine cancers of the prostate, breast, lung, and pancreas.
Correlogic has licensed the proteomic cancer test technology to LabCorp of Burlington, North Carolina, and Quest Diagnostics, in Teterboro, New Jersey. Both companies hope to make the test available through their laboratories throughout the United States by the end of the year or shortly thereafter.
In the meantime, FDA and NCI in cooperation with Correlogic are planning a series of clinical trials to assess how well the test performs in diagnosing and staging ovarian cancer and to seek FDA approval for the widespread use of the technology. Testing conducted by federally certified labs, such as LabCorp and Quest, does not require FDA approval.
The first trial, expected to begin within the next few months, will be conducted on 1500 women with a history of ovarian cancer to see whether the test can detect cancer recurrence.
The only available test for assessing ovarian cancer recurrence is the CA-125 test, which measures the levels of a biomarker, a protein called CA-125, in patients who have survived ovarian cancer. The CA-125 test is relatively insensitive in detecting ovarian cancer in early stages.
“CA-125 is miserable as a biomarker,” says Emanuel Petricoin of the FDA. “It's only good for telling you that you have a late-stage cancer. We want to see if the proteomic test can do better.”
The goal of the first trial is to show that the proteomic test can do at least as well as the CA-125 test in predicting cancer recurrence. The next step will be to conduct a trial to see whether the test can accurately discern between ovarian cancer and women who present with a benign pelvic mass.
“If a woman comes into a doctor's office with cramping, bloating, or swelling, she typically undergoes several rounds of tests,” says Petricoin. She may be given a pelvic exam, and ultrasound, and if it reveals a mass, she will eventually be given a laparoscopy to biopsy the tissue.
“By the time you get around to the laparoscopy, she could progress from stage I to stage II,” says Petricoin. “But if you could do a blood test at the same time as the ultrasound, you might prevent this from happening.”
Petricoin predicts that this trial could be completed within a year or two because researchers will know right away if the test successfully determines whether a pelvic mass is malignant.
If the initial studies are successful, Petricoin says the proteomic test will carried out in a clinical trial of women at high risk for ovarian cancer, for example those with a family history of the disease. Ultimately, the researchers hope to learn how well the test performs in screening the general population.
Correlogic is also developing future commercial distribution proteomic tests for other cancers, including prostate, breast, lung, pancreatic and colon cancers.
. . .