The finding means that a series of new anticancer drugs already in development are likely to work. They may work very well indeed, the study suggests.
When normal cells reach the end of their useful life, they self-destruct. This suicide process is called programmed cell death or apoptosis. But cancer cells have a defective self-destruct program. They make too much of a molecule called BCL-2, which gobbles up the chemical messengers that activate cell suicide.
Anthony Letai, MD, PhD, Stanley Korsmeyer, MD, and colleagues at Dana-Farber Cancer Institute wondered what would happen if they stripped cancer cells of their BCL-2 armor.
"What better way to kill cancer cells than targeting the molecules that directly control their survival?" Letai asks in a news release.
To see what would happen if cancer cells didn't have BCL-2 protection, the researchers created a strain of genetically engineered mice whose BCL-2 could be switched off by a common antibiotic. The mice also carried a gene that gave them leukemia.
By the age of 7 weeks, all 28 test animals had leukemia. All 14 mice that continued making BCL-2 died of leukemia by 100 days of age. But the 14 treated animals, who received the antibiotic in drinking water, had their BCL-2 cut off. All of them had fewer leukemia cells, and their white blood cells numbers became normal within days of therapy. Five of these mice lived for more than 200 days, and one lived for more than a year.
That's exciting news. Until this experiment, nobody was sure that simply removing the barrier to cell suicide would result in cancer-cell death.
"Abnormalities in genes affecting [programmed cell death] have been found in nearly every cancer, suggesting they may be necessary to develop cancer," Letai and colleagues write in the September 2004 issue of Cancer Cell.
Several drug companies are working on treatments that would block BCL-2. BCL-2 is crucial for proper immune function. But the mouse studies suggest that humans could tolerate a temporary BCL-2 block long enough for such future drugs to have an anticancer effect.
Senior study author Korsmeyer serves on the scientific advisory board of IDUN Pharmaceuticals, which is developing cell-death therapeutics.
SOURCES: Letai, A. Cancer Cell, September 2004; vol 6: pp 241-245. News release, Dana-Farber Cancer Institute, Boston.
By Daniel J. DeNoon
Reviewed by Brunilda Nazario, MD
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