MONDAY, Sept. 20, 2004 (HealthDayNews) -- Researchers say they have eliminated leukemia cells in mice by shutting off a molecule necessary for the cancer cells' survival.

Reporting in the Sept. 21 issue of the journal Cancer Cell, scientists said the experiment confirms that cancer calls cannot remain malignant in the absence of the molecule, known as BCL-2, which fights cell death. When it is shut off, the cancer cells self-destruct.

"Turning off BCL-2 is an effective thing to do if you want to kill cancer cells," said Dr. Anthony Letai, an instructor in medicine at Dana-Farber Cancer Institute in Boston and the study's lead author.

BCL-2 is a gene involved in cell function. But in excess amounts, it can inhibit a normal process within cells called apoptosis, whereby the body rids itself of unneeded or damaged cells that shouldn't be reproduced.

Cancer cells fight apoptosis, or programmed cell death, by making an overabundance of BCL-2. Scientists had suspected, but hadn't confirmed, that cancer cells need BCL-2 to survive.

To test the hypothesis, the Dana-Farber team genetically engineered mice to be highly susceptible to developing leukemia. The mice also were modified so that BCL-2 could be switched off by adding an antibiotic to the animals' water.

The researchers tracked 28 mice that developed leukemia at five to seven weeks of age. Half of them were given an antibiotic to turn off BCL-2; the others were not treated. Within three days, the treated mice had a decline in leukemia cells; within 10 days, their white blood-cell counts were normal. Five of the mice lived for more than 200 days, and one lived more than a year.

By contrast, all of the untreated mice died in just over 100 days.

"It's really elegant proof of what many in the research community have believed for a number of years, and that is pro-survival genes such as BCL-2 can perhaps both initiate and help drive the growth of cancer cells," said Alan Kinniburgh, senior vice president for research at the Leukemia & Lymphoma Society.

Scientists already are looking to develop new therapies that would kill cancer by targeting the BCL-2 gene. "If you can correctly target the defect in programmed cell death, you can directly induce death in these cancer cells," Letai said.

"This general strategy of targeting apoptosis, I hope, will be generalizable beyond leukemia and into solid tumors," he added, "but time will tell."

As yet, no such drug has been tested in humans. Drug therapies that block BCL-2 are five to seven years off, Kinniburgh predicted.

The hope is that BCL-2 blocking agents will be less toxic to normal human cells and better tolerated than chemotherapy, or perhaps could be a potent add-on to chemotherapy for some patients.

"If a drug of this sort needed the additional killing power of chemotherapy to be an effective treatment, that would still be a wonderful outcome for perhaps many cancer patients," Kinniburgh said.

More information

The National Cancer Institute has more on harnessing apoptosis to destroy cancer cells.

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