The Secrets Of A Cancer Cell's Success

JUST AS CHEMISTS ARE beginning to understand how substances in food prevent cancers from forming, other researchers are bearing down on the mechanics of malignancy itself In a seminal new study, published in the Proceedings of the National Academy of Sciences, U.S. and Canadian researchers reported that cells from human tumors produce an "immortalizing enzyme" called telomerase (pronounced tel-AH-mer-ace). The discovery won't affect clinical practice any time soon, but it suggests a whole new approach to cancer treatment. If telomerase proves as important as it now appears, curing cancer could be as simple-or as complicated-as blocking the enzyme's effect.

At the heart of the new finding is an obscure but powerful molecule known as the telomere (TEA-lo-meer). Telomeres are novel strands of DNA that cling like plastic shoelace tips to the ends of chromosomes, keeping them intact during the rough-and-tumble of cell division (chart). Every time a typical cell divides, its chromosomes lose a bit of telomere. When the telomeres are gone-typically after 50 to 100 cell divisions-the chromosomes start to fray and the cell withers and dies. When cancer cells start dividing uncontrollably, their telomeres quickly erode. But instead of vanishing completely, the shortened telomeres stabilize, and the cells keep right on growing.

How do cancer cells manage this feat? Researchers had shown in 1985 that single-celled organisms use the telomerase enzyme to generate new telomeres as their old ones are sloughed off, but no one had ever detected the enzyme in human tissue. So a team led by biologists Calvin Harley and Silvia Bacchetti set up an experiment to look for it. Working out of Ontario's McMaster University and the California-based Geron Corp., the team compared cells from advanced ovarian tumors with normal cells taken either from cancer patients or from healthy people.

The result was striking. Though none of the healthy cells produced telomerase, all of the tumor cells did. And as expected, the telomerase-rich cells maintained stable telomeres when the researchers let them grow for long periods in culture. The study was limited to ovarian cancer, but Harley says his group will soon report similar findings for other cancers as well.

The remaining challenge is to see whether blocking the action of telomerase would stop the process of malignancy. Theoretically, there couldn't be a more elegant approach to treatment. A drug that blocked the action of telomerase would presumably make cancer cells age and die naturally. And because normal cells (with the possible exception of sperm and egg cells) don't use telomerase, they would presumably escape any toxic effects. The catch, of course, is that no one knows how to make such a drug, because no one knows exactly how the enzyme works or is constructed. Scientists at the Geron Corp. are now screening myriad compounds in test tubes, hoping to turn up an effective telomerase blocker. Harley predicts they'll have something to test in people within three years. In the long run, he says, the study of telomeres could produce better treatments not just for cancer but for various age-related afflictions, from wrinkles to heart disease. Until then, though, a sense of irony may be the best medicine. For if immortal tumor cells don't kill us, age surely will.

Like plastic tips on shoelaces, telomeres keep chromosomes intact during cell division. But telomeres become shorter as cells age.

In a normal cell, the telomeres eventually erode completely. The chromosomes then disintegrate, and the cell dies.

Researchers have found that tumor cells use an enzyme called telomerase to stop the aging process. Because they never run out of telomeres, these cells can go on dividing indefinitely.

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