While most of the Early Detection Research Networks April meeting was devoted to setting ground rules for the network, talk bubbled over to several promising biomarkers.
Prostate specific antigen. Although not yet proven responsible for the recent decline in prostate cancer death rates, PSA is widely used as a biomarker. (According to the National Ambulatory Medical Care Survey, over 7 million men get PSA tests each year.) The downside: PSA is prostate, not cancer, specific. That means the test flags men without cancer, leading to unnecessary biopsies and surgery.
CA-125. This ovarian cancer blood marker detects more late stage than early stage tumors. High levels of CA-125 also occur during pregnancy and menstruation, and in the presence of endometriosis and benign ovarian tumors, confusing interpretation. Both PSA and CA-125 are under study in the 150,000 volunteer Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
LPA (lysophosphatidic acid). "LPA is probably the most accurate marker we have for detection of early stage ovarian cancer," said Northwestern Universitys David Fishman, M.D., who is heading a multi-center study of the marker. A 1998 report from the Cleveland Clinic found 9 of 10 women with stage I disease, 24 of 24 with advanced disease, and 14 of 14 with recurrent ovarian cancer had elevated blood LPA levels. In contrast, just 5 of 48 controls had elevated LPA. A growth factor, LPA is not generally present in normal ovary cells.
Telomerase. This enzyme, found in high levels in 90% of tumors, allows malignant cells to divide indefinitely. While most early tests measure telomerase in cells, William Highsmith, Ph.D., at the University of Maryland, is focusing on detecting the enzyme in blood, as a lung cancer marker. The catch: telomerase degrades quickly, perhaps too quickly for a practical test.
Mitochondrial DNA mutations. It turns out that mitochondria, the tiny power plants inside each cell, harbor identifiable mutations that could signal cancer. These telltale mutations appeared in urine, blood, and saliva samples from head and neck, bladder, and lung cancers, according to research published in the March 17, 2000 Science. David Sidranksy, M.D., who led the Johns Hopkins team, said, "Finding mitochondrial mutations is much easier [than finding nuclear DNA mutations]. With additional research, we expect to be able to identify mitochondrial mutations through a simple blood test."
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