[MOL] Aim to starve rather than poison [00305] Medicine On Line

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[MOL] Aim to starve rather than poison

Strategy aims to starve rather than poison cancer

BOSTON - AP World News via NewsEdge Corporation : The biggest thing in cancer is this little four-word sentence: Tumors make blood vessels.

It is not as obvious as it sounds.

For a long time, doctors assumed that spreading cancer makes do with the blood supply already in place. But no. Now they know that cancer grows its own.

This biologic insight has turned out to be among the precious few that opens an entirely new strategy for controlling a human ill. In the past two or three years, the discovery has become the starting point for the most studied, the most tested, and absolutely the most talked about endeavor in all of cancer research.

If it leads where scientists hope _ and where drug companies are placing big research bets _ then it should be possible to stop cancerous tumors by blocking their ability to launch the fresh blood vessels needed for survival. To kill a cancer, the thinking goes, starve it.

At this point, no one knows if it will work. But cancer experts say they cannot remember a time when there has been so much enthusiasm for a new approach to treatment.

The idea has taken more than 30 years to evolve from the universally scoffed-at brainstorm of Harvard surgeon Judah Folkman. Now it is an enterprise being chased by dozens of companies, ranging from the biggest pharmaceutical makers to one-idea startups.

At least 20 drugs that block the growth of blood vessels are in various stages of testing on people with cancer. More are nearly ready for testing. At the National Cancer Institute, Dr. James Pluda guesses that literally hundreds of other potential ones are in development.

``It's considered one of the hottest areas in all of medicine, not just cancer,'' he says. ``I'm not aware of any drug company, big or small, that is not working in this field.''

Cancerous tumors rely on the construction of new blood vessels _ a process scientists call angiogenesis _ to bring in oxygen and nutrients. Without this blood supply, they never grow larger than a pinhead. The question is whether any of the drugs in the works can thwart this basic biological process and thereby cure cancer, or at least stop it from spreading.

``The reason so many companies are interested in this is the possibility _ and I emphasize possibility _ that it will be broadly applicable to all tumor types,'' says Dr. Susan Hellmann, development director at Genentech.

In other words, if all kinds of cancer need new blood vessels, then one drug that interrupts this process might be good against all of them. With this in mind, drugs such as Sugen's experimental blood vessel blocker, SU5416, are being tested against cancers all over the body, including the colon, lung, kidney, ovaries, breast and skin.

Forty-four separate studies are under way with this one drug alone. It's even being tested against cancers of the blood, on the theory that even this malignancy requires the growth of fresh blood vessels in the bone marrow, where the cancer starts.

``These could be huge drugs, almost like the Holy Grail,'' says Peter Hirth, Sugen's president.

Doctors explaining their enthusiasm for this approach usually start by rhapsodizing over its elegant scientific underpinnings, worked out by Folkman and others who joined the field later. Then they mention the exceptionally promising experiments on rats and mice, in which tumors stop growing, shrivel up, even disappear . Finally, they get around to the miracles.

These amazing stories, the against-all-odds recoveries of people at death's door, are the most gripping and yet ephemeral of all the evidence in this young field. Most of the new compounds are in such early stages of testing, and their study subjects are so riddled with cancer, that no one can say with confidence whether the drugs do any good at all.

But a few of the terminally ill volunteers in these last-ditch experiments have suddenly gotten better. Even skeptics who have watched cancer breakthroughs come and go cannot help being intrigued.

Like most of those who have tried the new drugs, Clayton Twigg had failed all standard treatments and was dying. He had a rare and extremely aggressive form of thyroid cancer that had spread into his chest. At one point, his neck grew so big there was no indentation between chin and chest.

Unwilling to give up, Twigg volunteered for an experimental blood vessel blocker at University of Hospitals of Cleveland. In February, he became the eighth patient in a study of the safety of combretastatin, made by Oxigene.

``By the second treatment, bingo! The tumor had started to shrink,'' said Twigg, 56, an engineer from Westlake, Ohio.

By the end of six treatments, doctors could no longer see the growth on scans. In August, they decided to operate. But when they looked around his thyroid for remaining traces of cancer, there were none.

The news, though obviously good, does not mean Twigg has been cured. Undetectable cancer may lurk somewhere in his body. Still, his doctors say they have never heard of such a dramatic remission at Twigg's stage of this particular cancer.

Nevertheless, those who follow drug testing are reluctant to make too much of stories like this. Cancer is not an entirely predictable disease; people sometimes get better for no apparent reason. Furthermore, despite being terminally ill, those admitted to drug studies are often healthier than run-of-the-mill cancer patients, so they respond better to novel therapies.

``I don't want to give the impression this is a cure-all, the silver bullet for cancer,'' says Dr. Scott Remick, who heads Twigg's study. ``But there's no doubt this patient has had a very significant response.'' ^MORE<

Warmly, lillian
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