It is well known that between 1950 and the early part of this century, deaths due to cardiovascular insult dropped precipitously while cancer death rates were virtually unaltered. How can we change these dismal statistics?
According to Anna Lokshin, Ph.D., associate professor at the University of Pittsburgh Cancer Institute, “Cancer biomarkers serve many uses ranging from early detection to differential diagnosis to therapeutic monitoring. So because of its lethality in the later stages of the disease, we feel that it is critical to develop new and more effective screening tools.”
Given that the lifetime risk of ovarian cancer is 1.8%, an effective screening strategy must have a sensitivity of at least 80% and a specificity of 99.6% in the early stages of the disease. Dr. Lokshin and her colleagues have designed a serum multimarker panel using a group of well-known biomarkers, which for ovarian cancer yielded a sensitivity of 90% and a specificity of 98%. However, to be effective, higher sensitivity and specificity is required, so there is a need for biomarkers able to recognize preclinical disease at an earlier stage.
“This means we need to examine additional biomarkers, combine different classes of biomarkers, for example, proteins and nucleic acids, or look at biomarkers in other bodily fluids,” Dr. Lokshin concluded. Indeed, for a number of cancers, including ovarian, pancreatic, lung, and breast, marker levels in the urine of healthy individuals compared with that of cancer patients proved to be more accurate in terms of both sensitivity and specificity than in serum.
These studies, while tantalizing, leave open a number of questions for future investigations. This includes a need to verify the performance of expanded sets of serum biomarkers of these cancers while further optimizing the biomarker panels through combinations of serum and urine biomarkers.
Another strategy would be to develop recombinant antibodies that are optimized for urine biomarkers using selective screening of phage-display antibody libraries. Yet another approach would be to examine combinations of urine proteins with DNA isolated from urine or from microRNA.
An alternative task is to initiate prospective collection of matching urine/serum samples in symptomatic patients. Specifically included would be ovarian cancer patients with a pelvic mass, breast cancer patients who are positive on mammogram studies, lung cancers diagnosed through CT scan, and pancreatic cancer diagnosed by MRI. All these materials would be preserved for future validation.
But, perhaps the most challenging need is to convince the principle investigators of large-scale cancer screening trials to collect urine samples from their participants, given the fact that urine has been ignored by cancer researchers over the years as a source of diagnostic information.