Background
The human kallikreins are the largest group of genes of a subgroup of enzymes, known as the serine protease enzyme family. In 1999, only three members of this human gene family were known. Today, this gene family includes 15 members, seven of which have been discovered only recently. Prostate-specific antigen (PSA), the most famous member of the human kallikrein gene family, is the premier biochemical tumor marker used for diagnosing prostate cancer.
Kallikreins are expressed in many tissues throughout the body, including those that are hormone dependent, such as the testis, ovary and breast. A Canadian research team has recently shown that in addition to PSA, many new members of the human kallikrein family – such as hK5, hK6, hK7, hK8, hK10, and hK11 -- are likely suitable biomarkers for detecting ovarian, breast and prostate cancer. The investigators have also discovered that each of these family members is capable of diagnosing a fraction of ovarian cancer patients.
A New Study
Eleftherios P. Diamandis, M.D., Ph.D., FRCP, of the Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada is among the world's foremost authorities on kallikreins and cancer. Dr. Diamandis will be discussing his research -- including recently published papers on ovarian cancer biomarkers in the journal "Cancer Research" and the "Journal of Clinical Oncology" -- at the upcoming meeting of the American Association of Clinical Chemistry (AACC) being held July 20-24, 2003 at the Pennsylvania Convention Center in Philadelphia, PA. More than 16,000 attendees are expected.
A Theory of Excessive Enzymes
The discovery of the involvement of these enzymes in ovarian cancer stems from Diamandis' earlier exploration into whether other members of the kallikrein family cause a serum elevation that can be detected and monitored in cancer patients. He has discovered that the behaviors among the molecules in ovarian cancer were similar to the behavior of the molecules of PSA, albeit in different tissues.
While the mechanism by which kallikreins might be involved in ovarian cancer and/or its progression is not yet fully understood, he speculates that this family of enzymes constitutes a proteolytic cascade in ovarian cancer. He believes that with ovarian cancer the entire cascade is activated, members of the kallikrein family are upregulated, and the cancer cells produce higher amounts of the enzymes.
Methodology
His discoveries stem from retrospective examinations of stored serum samples collected 5-10 years ago by women with advanced stage ovarian cancer. Their samples included clinical information such as stage, grade, and survival rate. He and his research team correlated the levels of certain kallikreins with the clinical pathological findings and found that many of them were associated with unfavorable prognostic markers, such as late-stage or higher-grade disease. The researchers also discovered that patients who had higher elevations had shorter overall survival than those who had no elevation.
While these studies were based on patients with advanced stage disease, his new research focuses on women diagnosed with early stage ovarian cancer. Diamandis will examine whether or not the enzymes are elevated in the early stage of the disease as they are in later stages.
Assistance in Diagnosing an Elusive Cancer An early screening evaluation is done using the CA125 marker (a blood test for a tumor marker that is found in higher-than-normal levels among women with ovarian cancer) and an ultrasound. These methods are still not very sensitive in detecting early disease, so additional markers are required. Diamandis believes the markers he has identified will work in conjunction with CA125 and ultrasound to improve diagnosis and prognosis.
The work of Dr. Diamandis is supported by the Early Detection Research Network of NCI, USA, The National Institutes of Health, USA, The Natural Sciences and Engineering Council of Canada (NSERC), The National Cancer Institute of Canada (NCIC) and IBEX Diagnostics, Montreal, Canada.
Conclusions
New biomarkers for ovarian (and very likely other) cancers likely exist and need to be discovered, evaluated clinically and ultimately put together as a panel to obtain a diagnosis early and begin treatment. therapy. These newly identified serum biomarkers may be the key to earlier diagnosis and better prognosis for women with ovarian cancer.
The American Association for Clinical Chemistry (AACC) is the world's most prestigious professional association for clinical laboratorians, clinical and molecular pathologists, and others in related fields. AACC's members are specialists trained in the areas of laboratory testing, including genetic disorders, infectious diseases, tumor markers and DNA. Their primary professional commitment is utilizing tests to detect, treat and monitor disease.
Editor's Note: To schedule an interview with Dr. Diamandis, please contact
Donna Krupa at 703-527-7357 (direct dial), 703-967-2751 (cell) or djkrupa1@aol.com. Or contact the AACC Newsroom at: 215-418-2429 between 8:00 AM and 4:00 PM EST July 20-24, 2003.