Katie's Crusade

TED THAI FOR TIME
INSIDE VIEW: Dr. Moshe Shike of Memorial Sloan-Kettering conducts a guided tour of a patient's colon

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No one expects stories like Seguin's to make up for the loss Couric has experienced, but they do bring her a measure of satisfaction. "It's difficult every day without Jay," Couric says. "But it's not difficult to do this, because I feel that if I can save even one family the heartbreak that mine went through, it's worth it."

If you're serious about protecting yourself and your loved ones against colorectal cancer, it will help to know something about the disease. Nearly all colon cancers start as polyps, tiny grapelike projections that sprout on the inside of the large intestine. Most of the time these growths are benign, but occasionally a collection of cells--through a series of genetic mishaps--will get bigger and bigger until it turns into a tumor. About 25% of these malignant growths are triggered by a genetic predisposition that has been present since birth. The rest of the time, normal genes become damaged with age or exposure to the toxic brew of wastes that collect in the colon.

Researchers have identified the genes responsible for at least two types of hereditary colon cancer--dubbed FAP and HNPCC --that trigger malignant growths in folks in their 30s and 40s. But it can be tough to tell who has the genes, since they are often camouflaged by normal ones. Last month Dr. Bert Vogelstein and his colleagues at Johns Hopkins Medical School in Baltimore, Md., reported in the journal Nature that they have figured out how to unmask the defective genes. Meanwhile, researchers at Exact Laboratories in Maynard, Mass., have developed a simple stool test that will alert your doctor to any dangerous genetic changes in your colon. The test costs $250 and may become more widely available by the end of the year.

What if you could prevent the polyps from forming in the first place? In 1991 Michael Thun, an epidemiologist with the American Cancer Society, made an intriguing observation: people who regularly take aspirin are less likely to develop colorectal cancer. It turns out that aspirin blocks the production of an enzyme, called COX-2, that is found in 90% of all tumors and half of the polyps in the large intestine. Apparently most of these abnormal tissues need COX-2 to grow. Stop the production of the enzyme, and you might be able to prevent the cancer from getting larger--or from forming in the first place.

At least that's the idea. Since COX-2 is produced by normal cells as well, doctors may run into trouble if they try to shut down its production entirely. Also, taking aspirin on a regular basis can lead to other problems, like internal bleeding. Still, researchers are sufficiently intrigued by the COX-2 connection that they're trying to determine whether a new generation of seemingly safer drugs, called COX-2 inhibitors, can reduce the incidence of cancer among folks with the FAP or HNPCC genes. "It's a very exciting area of research," says Thun. "But it's too early for clinical application."

Surgery is still the front line of defense against colon cancer, and it is highly effective against the smaller tumors. (Better techniques mean that less than 2% of all colorectal-cancer patients now undergo a colostomy, in which the large intestine is rerouted to a hole in the abdomen and emptied into a bag. That's down from as many as 20% two decades ago.) Larger or more aggressive tumors usually require chemotherapy, which can be a problem. Whereas breast cancer, for example, often succumbs to any of eight to 10 powerful drugs, there has until recently been only one drug strong enough to battle colon cancer--a drug that was developed in the 1950s called 5-fluorouracil, or 5-FU.

The problem with having just one chemotherapy drug is that it limits your options. The cells that line the intestine are so used to acting as a garbage dump, explains Dr. Dennis Slamon of ucla, that the ones "that eventually become malignant are less susceptible to chemotherapy."

But there's good news on the chemotherapy front. In 1998 the Food and Drug Administration approved Camptosar (also called CPT-11) for the treatment of advanced stages of colon cancer, and using Camptosar and 5-FU in combination seems to be most effective. It's a potent cocktail that not all patients can tolerate, but it has, in some small studies, doubled short-term survival rates.

Looking to the future, researchers would like to take advantage of some of Mother Nature's own ideas to design new chemotherapy drugs. Scientists at Vion Pharmaceuticals of New Haven, Conn., are interested in co-opting a group of Salmonella bacteria that normally attack the intestines and cause dysentery. Salmonella, it happens, also happily infect all kinds of tumors, including colon cancer. By loading genetically crippled salmonella with one of the body's own cancer-fighting chemicals (a molecule called tumor necrosis factor), researchers at Vion hope to destroy or at least shrink a wide variety of cancers. Safety studies in humans are planned for later this year.