CBCRP-funded Researcher Receives Nobel Prize
Katherine McKenzie, Ph.D., Manager, Research Dissemination and Outreach
New ideas can become significant achievements when nurtured in the right conditions. In 1996, the California Breast Cancer Research Program funded Dr. Elizabeth Blackburn, at the University of California, San Francisco, for her idea of finding a way of using telomerase to treat breast cancer. Last month, she received the 2009 Nobel Prize in Physiology or Medicine for her work with telomerase and telomeres. Dr. Blackburn shares the award with Dr. Carol Greider of Johns Hopkins University School of Medicine and Dr. Jack Szostak of Harvard Medical School.
Telomeres and Telomerase in Tumor Cells
Every time a cell divides, its chromosomes shorten. The more a cell divides, the shorter the chromosomes become until the cell can no longer keep dividing, and the cell dies. This is normal cell function. Like the aglets that keep your shoelaces from unraveling, telomeres behave like caps on the ends of every chromosome. Telomerase is an enzyme that prevents the telomeres from shortening. It is found in immature eukaryotic cells and in a subset of normal adult cells—usually those that are rapidly dividing, like tumor cells.
One of the deadly elements of tumor cells is their immortality—in other words, their ability to continue dividing many more times than normal cells. The telomeres in these tumors do not seem to shorten enough to stop the tumor cells from dividing. For researchers exploring new treatment directions, one approach has been to look for ways to kill tumor cells by using their unique biological features against them.
Using Telomeres for Treatment of Breast Cancer
Dr. Blackburn’s initial project investigated strategies for treating breast cancers by taking advantage of their elevated telomerase status. In one strategy, she hypothesized that since both HIV and telomerase need to be able to decode DNA in order to function, the drugs that inhibit HIV might also inhibit the action of telomerase. The idea was that the drugs would turn off telomerase, which would in turn cause the tumor cells to stop dividing, effectively killing them. Some of the drugs were able to inhibit telomerase activity in the test tube, but the application in cells proved to be more complicated.
Another strategy that Dr. Blackburn explored involved turning the active telomerase against the tumor cell by causing them to make “toxic” telomeres. Telomerase uses the RNA available in the cells as building blocks to rebuild the telomeres every time the cell divides. In this approach, the tumor cells with active telomerase are given a mutant “toxic” RNA for rebuilding the telomeres. The normal cells, which do not have the active telomerase, would ignore the toxic RNA and divide normally. Dr. Blackburn found that tumor growth was inhibited when cells were given even small doses of the toxic RNA. With subsequent funding, she has refined the type of RNA and been able to demonstrate increased inhibition of tumor growth.
At the time of Dr. Blackburn’s CBCRP funding in 1996, the idea of using telomeres to treat breast cancer was unique and risky. The properties of telomerase in cancer cells weren’t fully understood at that point, and many basic research questions hadn’t yet been answered. With scant data to support her hypothesis, there was little indication that her research would return the results she wanted.
A Shared Commitment to Improved Treatments
Developing effective, low-toxic treatments was a major goal that drove the CBCRP’s creators when they established the program. Their unconventional vision for the program called for new approaches to achieving significant advances in breast cancer therapy. We developed the IDEA award as seed money to allow researchers to pursue the early stages of investigation. The approach may be risky, but the consequences for failure are monetary rather than human costs, and the potential impact for a successful new therapy is enormous.
The California Breast Cancer Research Program congratulates Dr. Blackburn and her colleagues for their outstanding achievement.
