Online Extra: The Miracle of Early Detection

Research aimed at creating better diagnostic tests may ultimately prove more important than huge drug-development efforts

The war on cancer has focused on searching for drugs that can cure the deadly disease. But that may be the wrong approach, says Dr. Bert Vogelstein, professor of oncology and pathology at Johns Hopkins University. Vogelstein fervently believes that cancer will be tamed during the next century. But the bulk of the progress won't come from drugs, he thinks. "If I had to bet, the reason why cancer won't be a problem in 100 years is because of prevention, not treatment," he says.

Prevention, after all, is how many of mankind's worst scourges have been conquered. Drugs still can't cure smallpox or polio. But these diseases have been wiped out by preventative vaccines. "There are still viral diseases that we can't cure any better than we did 100 years ago," says Vogelstein. "But in most cases, they're not a problem because we can prevent them."


  Similarly, the real gains in cancer will come from prevention and early diagnosis, Vogelstein believes. "All solid tumor cancers, if caught early, are curable -- every single one," he explains. "You can take them out with good old surgery. You don't need any fancy new drugs or gene therapy. All you need is a knife, a scalpel, and a good surgeon." And advances in laparoscopic surgery have made it possible to snip out small tumors with only a tiny incision.

The challenge, therefore, is spotting these cancers while they can still be completely removed by surgery -- that is, before they metastasize and spread through the body. It's a difficult task, requiring far better diagnostic methods than exist today.

Take the so-called prostate-specific antigen (PSA) test for prostate cancer. A high PSA score doesn't always mean that a man has prostate cancer. Nor does a low one mean that cancer isn't present. More important, even when it does correctly indicate that cancer is present, the PSA test doesn't tell doctors if the cancer is aggressive and dangerous or so slow-growing that no treatment is needed.


  That's why research aimed at creating better detection methods may ultimately prove more important than the current huge effort to develop new drugs. While these research efforts are tiny, some of them are beginning to bear fruit.

Vogelstein has discovered a series of genes that, when altered, lead to colon cancer. One of these key mutations is in a gene called APC that normally acts as a tumor suppressor. When the mutation occurs in a cell, it essentially takes the brakes off the cell's growth, causing a malignancy. Since the mutation precedes the cancer, Vogelstein reasoned, spotting it might be a telltale sign of a coming tumor. The precancerous cells -- or a very small tumor -- could then be surgically removed, bringing a complete cure.

Vogelstein knew that bits of DNA from cells in the colon are shed in fecal matter. So he developed a sensitive test to look for DNA mutations in stool. Early results are promising. In the first feasibility trial, published early this year, Vogelstein looked for mutations in the stools of 28 patients with early-stage colon cancer, 18 patients with adenomas (benign tumors that often turn malignant), and 28 healthy people.


  "We wanted to test the most difficult cases, so we chose patients with early-stage cancers and those with pre-malignant cancers, both of which could in principle be cured by routine surgery if they were detected early," says Vogelstein.

The test spotted APC gene mutations in 61% of the patients with cancer and in 50% of the patients with adenomas. Significantly, none of the healthy people had the mutation. That means the test may not raise false cancer alarms.

Vogelstein is now planning a large-scale trial with thousands of patients. At the same time, he's trying to reduce the cost of the test, now about $500 per patient. The approach is licensed to Exact Sciences Corp. (EXAS ) in Maynard, Mass.


  However, few companies are interested in developing such tests. Detection just isn't sexy, compared to new drugs. Spotting pre-malignant adenomas in dozens of people -- and thus keeping them from getting cancer in the first place -- "is not nearly as dramatic a finding as if we had developed a drug that would have taken two of those patients with colon cancer and make them live a year longer," Vogelstein laments.

Newsmagazines put new drugs on the cover, not better detection technologies. What's more, far less money can be made selling a $100 test than marketing a cancer drug that costs $10,000 or more per year.

That's unfortunate, Vogelstein says, because other innovative ideas for spotting cancers early are popping up. One scientist at Johns Hopkins has been able to detect lung cancer by looking for mutations in sputum. And a recent paper in the medical journal The Lancet describes a way to use a tiny tube to collect fluid from women's breasts to look for telltale genetic alterations.

Despite the hurdles, however, these efforts are slowly moving forward. And ultimately, they may prove to be the key to finally taming cancer.

By John Carey in New York

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