Cancer : The wound That Never Heals

Back in the 1860s, renowned pathologist Rudolf Virchow specu-lated that cancerous tumors arise at the site of chronic inflammation. A century later, oncologists paid more attention to the role that various genetic mutations play in promoting abnormal growths that eventually become malignant. Now researchers are exploring the possibility that mu-tation and inflammation are mutu-ally reinforcing processes that, left unchecked, can transform normal cells into potentially deadly tumors.

How might that happen? One of the most potent weapons produced by macrophages and other inflamma-tory cells are the so-called oxygen free radicals. These highly reactive mol-ecules destroy just about anything that crosses their path-particularly DNA. A glancing blow that damages but doesn't destroy a cell could lead to a genetic mutation that allows it to keep on growing and dividing. The abnormal growth is still not a tumor, says Lisa Coussens, a cancer biolo-gist at the Comprehensive Cancer Center at the University of Califor-nia, San Francisco. But to the im-mune system, it looks very much like a wound that needs to be fixed.

"When immune cells get called in, they bring growth factors and a whole slew of proteins that call other inflamma-tory cells," Coussens explains. "Those things come in and go 'heal, heal, heal: But instead of heal-ing, you're 'feeding, feeding, feeding.' "

Sometimes the reason for the initial inflammatory cycle is obvious-as with chronic heartburn, which continually bathes the lining of the esophagus with stomach acid, predisposing a person to esophageal cancer. Other times, it's less clear. Scientists are exploring the role of an enzyme called cyclo-oxygenase 2 (cox-2) in the development of colon cancer. cox-2 is yet another protein produced by the body during inflammation.

Over the past few years, researchers have shown that folks who take daily doses of aspirin-which is known to block cox-2-are less likely to develop precancerous growths called polyps. The problem with aspirin, however, is that it can also cause internal bleeding. Then in 2000, re-searchers showed that Celebrex, another cox-2 inhibitor that is less likely than as-pirin to cause bleeding, also reduces the number of polyps in the large intestine.

So, should you be taking Celebrex to prevent colon cancer? It's still too early to say. Clearly Cox-2 is one of the factors in colon cancer. "But I don't think it's the ex-clusive answer;" says Ray DuBois, director of cancer prevention at the Vanderbilt--Ingram Cancer Center in Nashville, Tennessee. "There are a lot of other components that need to be explored:"

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