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| Winter 1999-2000 issue | . | Tamoxifen: Prescription for trouble? | |
LINKS: Biological Sciences at Notre Dame |
Could the most widely prescribed anti-cancer drug be a curse
as well as a blessing? The question nags Martin Tenniswood and drives his research. For more than 20 years tamoxifen has been used successfully and safely to shrink breast tumors. Last year it was approved as a preventative for women at high risk for breast cancer. Research shows that women with early-stage breast cancer who take tamoxifen are only half as likely to have their other breast become cancerous. But a debate now swirls around whether healthy women should be taking the drug. Scientists believe that breast cancer is related to exposure to the hormone estrogen. The more exposure, the more likely one is to fall victim to the disease. Tamoxifen works by blocking the effects of estrogen. When you interfere with normal hormonal responses, breast cancer cells die and the tumor shrinks. But Tenniswood, Notre Dame’s Coleman Professor of Life Science, says the drug may not be as good a preventative as has been thought. "It may result in the women developing a more aggressive form of breast cancer later on. The evidence we have in the lab says that this is, in fact, what happens with tamoxifen. "We presume that the response we’re seeing of having some cells survive and become invasive is due to tamoxifen’s estrogenic behavior. But we haven’t established that," he adds. "We’re trying to work out what the drug is doing, what genes it is turning on. Essentially, we want to kill the tumor cell without turning on the genes that cause it to become invasive." Tenniswood and his colleagues have developed an idea of how the drug works. Tamoxifen kills most but not all the tumor cells, he explains. In those cells that don’t die, it appears the drug backfires, causing them to produce substances that induce cell survival and also an enzyme that "chews up" material around the cell. Normally, dying cells produce the enzyme, causing the tumor to shrink. When surviving cells produce it, trouble results. Metastatic cancer cells, the most dangerous kind because they spread throughout the body, produce high levels of this enzyme, Tenniswood explains. It allows them to invade other tissue. — John Monczunski |
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