Research being published Saturday in the journal Cancer Research shows that the enzyme COX-1, and not the COX-2 enzyme, which is a current target of therapy, is expressed in epithelial ovarian cancer tissue samples isolated from women.
This finding, by researchers at Vanderbilt University Medical Center in Nashville, may suggest a new direction in cancer care -- using drugs that aim to block both COX-1 and COX-2 or drugs that block COX-1 alone. "This could have a significant clinical impact with regard to our thinking about ovarian cancer," said co-investigator Raymond DuBois, M.D., Ph.D.
Ovarian cancer is the most lethal gynecological malignancy worldwide. The American Cancer Society estimates 25,400 new cases in the U.S. in 2003; more than half will die of the disease because it has few symptoms and is usually not detected until it is well advanced. The new research may help stop the cancer quicker.
"To our surprise, in this pilot study we found that COX-1 was the predominant cyclooxygenase isoform expressed in ovarian cancers and that a selective COX-1 inhibitor could block the pro-angiogenic effects of COX-1 in ovarian cancer cells," said DuBois, the Mina Cobb Wallace Professor of Gastroenterology and Cancer Prevention at the Vanderbilt-Ingram Cancer Center.
"Some investigators have been considering treating women with ovarian cancer with COX-2 selective inhibitors," DuBois said. "In some cases the inhibitor might not work because most of the tumors evaluated in our study lack COX-2. Hence, it may be better to look at a selective COX-1 inhibitor or a non-selective inhibitor which would block both COX-1 and COX-2."
DuBois and S.K. Dey, Ph.D., the Dorothy Overall Wells Professor of Pediatrics and professor of Cell and Developmental Biology and Pharmacology, studied 11 tissue samples from women diagnosed with ovarian cancer and nine normal tissue samples. The cancerous tissues had not been exposed to chemotherapy, which is known to induce COX-2 expression.
"Significant levels of COX-1 or COX-2 were not detected in any of the normal human ovarian tissue," the scientists wrote. "However, dramatic elevations of COX-1, but not COX-2, protein and mRNA were detected in a majority of the ovarian cancer samples tested."
Dey, director of Vanderbilt's division of Reproductive and Developmental Biology, specializes in the area of reproductive biology, where his other research underway has improved out understanding of female infertility. He is a recipient of an NIH MERIT award.
DuBois is an expert on the COX enzymes and is a member of the National Cancer Institute's Board of Scientific Advisors. He was also awarded the 2002 Richard and Hinda Rosenthal Foundation Cancer Research Award by the American Association of Cancer Research for translational research that has made, or promises to soon make, a notable contribution to improved clinical care in the field of cancer research.
Their research was funded by the NIH, the T. J. Martell Foundation and the National Colorectal Cancer Research Alliance.
Vanderbilt University Medical Center, a top-20 NIH-funded research center and a U.S. News & World Report "Honor Roll" institution, is a major referral center for the Southeast and nation. It is made up of Vanderbilt University Hospital, The Vanderbilt Clinic, Vanderbilt Medical Group, Vanderbilt Children's Hospital, Vanderbilt School of Medicine, Vanderbilt School of Nursing and Vanderbilt-Ingram Cancer Center. Its faculty members have been awarded two Nobel Prizes for Medicine.
Journal
Cancer Research