Correction Appended

Within a year, if all goes well, the first cancer patient will be injected with two new drugs that can eradicate any type of cancer, with no obvious side effects and no drug resistance -- in mice.

Some cancer researchers say the drugs are the most exciting treatment that they have ever seen. But then they temper their enthusiasm with caution, noting that the history of cancer treatments is full of high expectations followed by dashed hopes when drugs with remarkable effects in animals are tested in people.

Still, the National Cancer Institute has made the drugs its top priority, said Dr. Richard D. Klausner, the director. Dr. Klausner called them ''the single most exciting thing on the horizon'' for the treatment of cancer.

''I am putting nothing on higher priority than getting this into clinical trials,'' Dr. Klausner said. The mouse studies are ''remarkable and wonderful,'' he said, and ''very compelling.'' But he pointed out that the studies were in mice and so, when it comes to humans, he said he wanted to emphasize ''the if's.''

The new drugs, angiostatin and endostatin, work by interfering with the blood supply tumors need. Given together, they make tumors disappear and not return.

Dr. James M. Pluda, who is directing the cancer institute's planned tests of the drugs in patients, said he and others at the institute were ''electrified'' when they heard the drug's discoverer deliver a lecture about the newest results. ''People were almost overwhelmed,'' Dr. Pluda said. ''The data were remarkable.''

Although the discovery of the drugs, and some of their effects, have been reported over the past few years, Dr. Pluda said that ''if people understood how many steps ahead'' the research was compared to what had been published, ''they'd be even more in awe.''

But Dr. Jerome Groopman, a cancer researcher at the Harvard Medical School, was wary. ''We are all driven by hope,'' Dr. Groopman said. ''But a sober scientist waits for the data.'' And until the drugs are given to humans, he said, the crucial data simply do not exist.

So far, the drugs are the only ones ever tested that can seemingly eradicate all tumors in mice, even gigantic ones, equivalent to a two-pound growth in a person. The best that other cancer drugs have done is slow the growth of these large tumors. Mice are the traditional test animals in cancer research.

But even the drugs' discoverer, Dr. Judah Folkman, a cancer researcher at Children's Hospital in Boston, is cautious about the drugs' promise. Until patients take them, he said, it is dangerous to make predictions. All he knows, Dr. Folkman said, is that ''if you have cancer and you are a mouse, we can take good care of you.''

Other scientists are not so restrained. ''Judah is going to cure cancer in two years,'' said Dr. James D. Watson, a Nobel laureate who directs the Cold Spring Harbor Laboratory, a cancer research center on Long Island. Dr. Watson said Dr. Folkman would be remembered along with scientists like Charles Darwin as someone who permanently altered civilization.

The long trail to the discovery of the new drugs began more than 30 years ago when Dr. Folkman became obsessed by what many saw as a quixotic notion: that cancers cannot grow beyond the size of a pinhead unless they have their own blood supply. If he could block a tumor's blood supply, he reasoned, the tumor should shrink to a minuscule size.

The first major break in the efforts came a decade ago when Dr. Folkman and his collaborators found drugs that did what he envisioned. He called them anti-angiogenesis drugs because they stopped the process of developing new blood vessels, or angiogenesis. They slow tumor growth in animals but do not eradicate the tumors. Early results in patients indicate that the drugs may slow human cancers. Dozens of companies are developing such drugs.

The results with these weaker drugs were ''a proof of principle,'' said Dr. Bart Chernow, a professor of medicine and dean for research and technology at the Johns Hopkins University School of Medicine. Dr. Chernow is a founder of Entremed, a company in Rockville, Md., that was formed to make and market angiostatin, endostatin and other weaker drugs that can slow cancer growth.

But the real breakthrough -- and the two new drugs -- came from Dr. Folkman's efforts to understand a peculiar phenomenon that has been known to cancer surgeons for 100 years: sometimes a patient will have a single tumor, with no evidence whatsoever of metastases, the satellite cancers that can pepper a patient's body. A doctor will remove the tumor and all will seem fine. But then, a few months later, a whole series of metastases will appear, grow, and kill the patient.

In 1989, Dr. Folkman proposed a reason for the effect, which he wrote on a large white board in a room where his laboratory group had its weekly seminars. Is it possible, he asked, that a tumor could be making both stimulators and inhibitors of blood vessel growth? If so, the inhibitors might travel through the bloodstream, squelching metastases. When the large tumor was removed, it would no longer be a source of inhibitors, allowing the tiny metastases to proliferate.

Dr. Folkman tried to get one of his doctoral or post-doctoral students to work on that idea. ''Each Friday, at our meeting,'' he said ''I would say, 'Here's a great experiment.' But no one wanted to work on it.'' It seemed too wild, Dr. Folkman said, too unlikely to result in findings that would end up in a scientific journal, a major goal of young scientists.

Undertaking The Big Challenge

Then, in 1991, a post-doctoral student, Dr. Michael O'Reilly, decided to take on the challenge. Dr. O'Reilly focused on a particularly deadly mouse cancer that grows to the equivalent of a two-pound tumor in a person.

As long as mice had the large tumor, they had no signs of metastases. But five days after the tumors were surgically removed, metastases invariably sprang up in the animals' lungs. Within 15 days, the animals would be dead, their lungs packed with large red tumors, like grapes.

Eventually, after arduous work in collaboration with chemists, Dr. O'Reilly discovered that the large tumors made a substance that stymied the growth of other tumors. This substance showed up in the animals' urine, but was present in such minute quantities that Dr. O'Reilly had to collect 10 quarts of mouse urine to obtain 30-thousandth of an ounce of the mysterious substance. It turned out to be a piece of a larger and very common protein, plasminogen, that the body uses in blood clotting. Dr. Folkman named the new substance angiostatin.

Apparently, cells can use the plasminogen gene for two purposes: they can use it at its full length to make plasminogen, or they can use just a piece of it and make angiostatin. Plasminogen does nothing to stop tumor growth. The question was, would angiostatin?

Dr. Folkman and Dr. O'Reilly discovered that angiostatin also appears, in minute quantities, in human blood. Using outdated human blood discarded by the Red Cross, they extracted enough angiostatin to treat mice. Then they began their experiment.



A Jubilant Celebration And a Second Discovery







Drug Combination Knocks Out Tumors




For the past four years, Dr. Folkman said, he and his colleagues have found that all tumors responded to the drugs in the same way. Even leukemia, a blood tumor, responds, he said, because it turns out that leukemia needs to form new blood vessels in the bone marrow to grow. Leukemia tumors grow on these blood vessels, ''like berries on a bush,'' Dr. Folkman said, shedding cancer cells into the blood.

But Dr. Folkman is the first to urge caution in leaping to conclusions about what might happen when patients try the drugs. ''Going from mice to people is a big jump, with lots of failures,'' he said.

Hopes were high for chemotherapy drugs that worked well in mice but turned out to be less successful in people. Therapies that used the immune system to rid the body of cancer also worked in mice but were disappointing when they were tried in people. Gene therapy treats mouse cancer, but has had limited success in people.

From bitter experience, most cancer researchers have learned to be leery of what one called ''that four letter word'' -- cure.

Meanwhile, Entremed is working as fast as it can to produce angiostatin and endostatin for studies in humans. Dr. John Holaday, Entremed's president and chief executive, said his company was working with the Bristol-Myers Squibb Company to develop angiostatin and had not yet decided on a corporate partner to develop endostatin. The drugs are being made in genetically engineered yeast growing in 20-gallon vats.

Dr. Pluda, of the cancer institute, said the first patients to get the drugs would have cancers that were growing quickly and were essentially untreatable. The institute will start by giving the drugs separately by the end of the year, he said, then hopes to combine them.

Already, Dr. Folkman said, he gets hundreds of calls a day from cancer patients, pleading for the drugs.

Dr. Folkman, in an interview on Friday, said one call had come from an old friend from medical school with prostate cancer that had spread to his bones.

''He's terrified,'' Dr. Folkman said. But there were no strings Dr. Folkman could pull. He said he had to tell his friend what he told all the other callers: ''You can't get it because it isn't being made.''

Photo: Dr. Judah Folkman is cautious about his cancer-drug discovery. (Children's World)(pg. 34) Diagram: ''IN THE WORKS: Hope for a Breakthrough'' Drugs called angiostatin and endostatin occur naturally in small quantities in the human body and work by interfering with the blood vessels that tumors need to survive and grow. When tested together in mice, the drugs made tumors disappear and not return. Mice are injected with cancer Cancer grows into large tumors on the back. Mice injected with salt water -- In this group, cancer continues to grow. Mice injected with either endostatin or angiostatin -- Cancer shrinks to almost nothing, but when treatment stops, the cancer may return. Mice injected with both endostatin and angiostatin -- After several weeks of injections, the cancer shrinks to nothing and does not recur. (Sources: Dr. Michael O'Reilly, Dr. Judah Folkman, Dr. Thomas Boehm and Dr. Timothy Browder)(pg. 34)