Commentary: Of Mice, Men, And Cancer Cures

This is a cautionary tale about the confusion that can erupt when you mix a powerful newspaper, desperately ill cancer victims, hungry investors looking for the next blockbuster drug, and the word "cure."

Last November, Judah Folkman and Michael S. O'Reilly--doctors at Boston Children's Hospital--reported in the science journal Nature that they had discovered two human proteins, called angiostatin and endosta-tin, that eradicated all signs of cancer in mice. The proteins were isolated from the urine of mice that had been given human cancers. The Nature report generated a buzz in the oncology community because it described a treatment that appeared to short-circuit the method by which tumors grow and spread throughout the body.

Since then, EntreMed Inc., a tiny biotech company in Rockville, Md., has been quietly working on a manufacturing process that would create enough of the two proteins to conduct human trials, which they hope to start in a year or two. Many news outlets ran stories about Folkman and O'Reilly's work, including Newsday, CNN, the Associated Press, Consumers Digest, BUSINESS WEEK--and The New York Times. The research has also been discussed at a handful of cancer meetings, the most recent a New York Academy of Sciences symposium on Apr. 28, to which the press was invited.

On the following Sunday, May 3, The New York Times revisited Folkman's discovery. But this time, they gave it the star treatment. The newspaper published a front-page story on angiostatin and endostatin, quoting Nobel laureate James D. Watson, a co-discoverer of DNA, saying that "Judah [Folkman] is going to cure cancer in two years."

The story, coming after a week of stock-market frenzy over Pfizer Inc.'s impotence blockbuster Viagra, caused a worldwide sensation. On Monday morning, EntreMed's stock shot up from $12.06 a share to a mind-boggling $85 before closing at $51.81 on May 4. EntreMed's phones were ringing off the hook, and cancer centers around the country were inundated with calls from patients desperate for the new "life-saving" drugs.

The only problem: There are no drugs. There may never be any drugs. So far, these proteins have only cured cancer in mice. And it's a long way from success with mice to a cure for humans, cautions Dr. James M. Pluda, senior clinical investigator of the National Cancer Institute's investigational drug branch: "The field of oncology is littered with the bodies of agents that were the next magic bullet."

"TAKE-HOME MESSAGE." To their credit, EntreMed and Folkman started putting that same message out within a day of the Times story, trying hard to end speculation that they had discovered a cancer cure. "We're very cautious about that four-letter word," EntreMed Chief Executive Officer John W. Holaday said over and over, and the stock dropped to 31 1/8 by May 6. But his cautionary message was still difficult to hear over the public's clamor for the new miracle drug. "All of a sudden, you pick up the newspaper and see a Nobel laureate saying there's a cure for cancer on the front page," says Lehman Brothers Inc. analyst C. Anthony Butler. "That was the take-home message."

The message arrived when the public and Wall Street were exquisitely tuned to hints of the next wonder drug. Pfizer's stock has climbed 50% since early this year on expectations of billion-dollar sales for Viagra. In April, the stocks of Zeneca Group PLC and Eli Lilly & Co. scored on news that their designer estrogen drugs, Tamoxifen and Evista, can prevent breast cancer.

But those drugs are already on the market, after numerous clinical trials. Angiostatin and endostatin, like so many promising lab discoveries before them, may never even reach human trials. "A lot of new investors don't have a very sophisticated understanding of the pitfalls involved in creating new drugs, especially cancer treatments," laments Volpe Brown Whelan analyst David M. Steinberg.

Reporters, analysts, and especially Nobel scientists must be far more careful about overhyping so-called cancer cures--particularly ones that are still more theory than reality. Granted, The New York Times published a story a day after its Sunday bombshell cautioning that it will be years, if ever, before the EntreMed treatments are commercially available. But that second-day hand-wringing is cold comfort for the millions of cancer victims whose hopes were raised by a "miracle cure" that might never materialize.

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