Turning a Tumor's Lights Off

When Olympic sprinters push themselves to the limit, the energy-producing pathways in their cells switch gears, turning to an oxygen-free pathway to keep the juice flowing. Cancer cells also use this pathway--called anaerobic glycolysis--even when there is plenty of oxygen around. Now, researchers have found that blocking a key enzyme involved in anaerobic glycolysis significantly slows the growth of tumors. The findings, say experts, suggest a new way to target cancer with drugs.

In 1924, German biochemist Otto Warburg first described how cells shift to anaerobic glycolysis when they become cancerous, and the "Warburg effect" has intrigued cancer biologists ever since. One possible reason for the shift is that tumors must sometimes cope with a lack of oxygen, or hypoxia--hence the need for anaerobic energy production. Warburg and later scientists postulated that interfering with glycolysis might be a way to treat cancer. In 1997, molecular biologist Chi Dang of Johns Hopkins Medical School in Baltimore, Maryland, found that blocking one enzyme involved in glycolysis, lactate dehydrogenase A (LDH-A), could slow the growth of cancer cells in petri dishes.

Now cancer researchers at Harvard Medical School in Boston, Massachusetts, have shown that blocking LDH-A, using a technique called RNA interference (ScienceNOW, 10 November 2004), lowers the growth rates of cancer cells by about 100 fold. Furthermore, when the team, lead by cell biologist Valeria Fantin, implanted LDH-A-normal cancer cells and LDH-A-deficient cancer cells in mice, LDH-A-deficient tumors grew more slowly and took two-and-a-half times longer, on average, to kill the mice than LDA-A-positive tumors. "We were really amazed at the differential growth rate of these tumors," says Fantin, whose team publishes its findings in this month's issue of Cancer Cell.

Dang agrees, calling the new results "dramatic." Fantin suspects that the risk of toxic side-effects will be low because case studies have shown people without functioning LDH-A are nonetheless healthy. But Dang cautions that any drug will have to hit LDH-A and not LDH-B, which may be important for heart function.

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