New Molecule Stops Cancer's Spread

FRIDAY, Sept. 2 (HealthDay News) -- A new way of killing cancer cells has been effective enough in animal studies to move into human trials, researchers report.

The method of attack is to block the activity of an enzyme called telomerase, which keeps cancer cells alive and growing, said Dr. Jerry Shay, lead author of a report on the animal work in the Sept. 1 issue of Cancer Research.

The study is an example of how seemingly esoteric basic science can be turned into clinical treatment for human disease. In this case, biologists have studied something called the telomere, a unit at the end of chromosomes, the cellular entities that carry genetic information.

In normal cells, the telomeres get shorter as cells divide and age. When they get short enough, the cell stops dividing. But that doesn''t happen in cancer cells, because telomerase prevents the telomeres from getting short, so the malignant cells continue their ultimately fatal growth.

"Over the years, what we have seen in screening a number of different human tumors is that telomerase is turned on in 90 percent of human cancers," Shay said. "We''re trying to find ways of inhibiting this enzyme."

A number of approaches have been tried, including a telomerase vaccine, he said. The attack described in the new report uses a synthetic molecule, made up of 13 nucleotides, the basic building blocks of genes, that prevents telomerase from reaching the cell.

The study led by Shay, who is professor of cell biology at the University of Texas Southwestern Medical Center at Dallas, centered on lung cancer that was artificially induced in mice by injecting malignant cells into their tails. Lung cancer survival rates are low, primarily because the malignancy spreads out of the lungs, metastasizing in other parts of the body.

The study showed that the telomerase-blocking molecule, designated GRN163L, stopped the spread of cancer into the lungs of the mice.

"What makes this an important observation is that this is the first time this particular drug has been shown to prevent metastasis into the lungs," Shay said. "So, it might prevent lung cancer cells from leaving the lung, and it might be able to prevent metastasis in other tumors."

The clinical trial will be conducted by Geron, the California-based biotechnology company that developed GRN163L. Geron received approval for the trial from the U.S. Food and Drug Administration in June. It will be conducted at two medical centers in New York, which are recruiting patients with chronic lymphocytic leukemia.

The primary purpose of the trial is to test the safety of the drug. If it is successful, it will be followed by a series of human trials to determine the effectiveness of the medication.

If all goes well, Shay said, GRN163L will ultimately be used as part of a combined treatment program. "Where this would pay off is for people who have a relapse after chemotherapy, after surgery," he said. "It would be used in combination with other therapies."

More information

The telomere/telomerase story is told in depth by the University of California, Los Angeles.

SOURCES: Jerry Shay, M.D., professor, cell biology, University of Texas Southwestern Medical Center, Dallas; September 2005 Cancer Research