Pulling the Plug on Cancer

The fountain of youth that keeps cancer cells immortal can be turned off by a mutated enzyme, researchers say.

The key to cancer cell immortality are the cell's telomeres, repetitive stretches of DNA at the ends of chromosomes that may protect the chromosomes when they divide. Researchers have learned that telomeres grow shorter and shorter each time a cell divides; once they're gone, the cell dies. Cells in sperm, bone marrow, and other tissues that divide frequently make an enzyme called telomerase that prevents telomeres from shrinking. Because cancer cells also make telomerase, scientists have suspected that the enzyme allows cancer cells to keep on dividing without dying. Many labs are testing whether compounds that block the enzyme can slow the growth of tumors.

Oncologists William Hahn, Robert Weinberg, and colleagues at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, mutated the gene for one part of the enzyme and inserted it into cultured human cells from colon, ovary, and breast tumors. The mutant unit bound with other building blocks of telomerase to create a dud enzyme that supplanted the native enzyme. Within 7 weeks, all cells had stopped dividing, the scientists report in the October Nature Medicine. In another clue that cancer cells persist because they maintain their telomeres, those cells that started out with longer telomeres in the experiment lived longer than those with shorter telomeres.

The findings are "an exciting step forward in the validation of telomerase" as a cancer drug target, says Louis Zumstein, a molecular biologist at Introgen Therapeutics in Houston, Texas. But an antitelomerase drug would be no magic bullet, as it would allow the cancer cells to continue dividing until their telomeres were gone. Such a lag time, says Hahn, could allow cancer cells to develop resistance to a drug by finding some other way to maintain their telomeres. The wisest approach, Zumstein says, would be to pair a telomerase inhibitor with additional drugs.

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