Controlling enzyme activity in ovarian cancer may lead to effective antitumor drugs
New research findings suggest that drugs which specifically inhibit enzyme activity could limit the lifespan of ovarian cancer cells and most significantly, have little or no toxic drug side-effects on other major organ systems in the body, including the digestive tract. National Institute on Aging (NIA) grantee Dr. Calvin B. Harley, currently at Geron Corporation, and his colleagues at McMaster University in Ontario, Canada, examined ovarian cancer cells in both the petri dish and in living organisms and found that the end regions of cancer cell DNA (the telomeres) were being stabilized with the aid of an enzyme called telomerase, which helped the tumor cells multiply out of control. The researchers hypothesize that if this enzyme activity could be inhibited through drugs or other mechanisms, then the tumors will cease to grow.
Dr. Huber Warner, deputy associate director for the NIA Biology of Aging program says, "These findings arose from basic research and give us a better understanding of the control of cell doubling and its relevance to aging. To me, the excitement here is finding a way to develop a cancer treatment that avoids the dreadful side-effects of many of the drugs we have now. In any drug therapy, targeting is an important issue. Since this enzyme activity is seen only in cancerous and reproductive cells, noncancerous cells in the body, such as those normally found in the liver or kidney, would not be affected by a possible therapy that could inhibit ovarian cancer cell growth."
Cancerous cells are capable of many more doublings than normal cells, and their doubling limit is regulated by the cell's DNA. The end regions of DNA are called telomeres, and normally function in maintaining the structural stability of the DNA double helix. As a person ages, their telomeres shorten, leading to lessened cell doubling. In cancerous ovarian cells, this telomere shortening occurs, but an enzyme called telomerase is activated which blocks further telomere shortening, thus allowing the cancer cells to continue to grow and multiply, leading to ovarian tumors.
Dr. Harley's co-researchers were Christopher M. Counter, Dr. Hal W. Hirte, and Dr. Silvia A. Bacchetti. Their findings appear in the April, 1994 issue of the Proceedings of the National Academy of Sciences, Vol. 91. Dr. Warner will be available to explain these latest findings and give a broad perspective on the research.
The National Institute on Aging is the major federal funding agency for age associated diseases. Please call (301)496-1752 for further information and to arrange interviews.