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Compound Interest

What if the way to win the war on cancer is not to cure tumors but to keep them from forming in the first place? Dartmouth's Michael Sporn, known as "the father of chemoprevention," has devoted his career to that question. Now he and his collaborators have two compounds in clinical trials—compounds that may stop tumors before they start.

By Jennifer Durgin

What is a healthy mouse?" It's a simple question that Dr. Michael Sporn poses to the hundreds of scientists gathered in the huge conference hall. He answers it by flashing a photo of healthy-looking mice on the giant screens beside the stage. Even if one injected the animals with a potent carcinogen, Sporn continues, for weeks afterward anyone would say the mice still looked healthy. He puts up another photograph of perky mice to prove the point.

"But," he goes on, "could these mice get life insurance . . . because all their lungs look like this nine months later?" The giant screens now display four mouse lungs covered with white tumors. The mice may have looked fine for weeks after the injections, Sporn points out, but "some very nasty things" were happening inside their bodies.

Now he drives his metaphor home, asking, "What is a healthy person?" Is someone who shows no outward signs of disease necessarily healthy? "No," argues Sporn, who is the Oscar M. Cohn '34 Professor of Pharmacology and of Medicine at Dartmouth Medical School.

Like an avalanche, a cancer may seem like a single event set in motion by a single trigger. But both cancers and avalanches are the result of a whole progression of unstable conditions. Long before a tumor forms, it begins as a group of abnormal cells caught in the wrong place at the wrong time. A whole network of cell-to-cell and tissue-to-tissue communications must go awry—resulting in cell differentiation, proliferation, and motility taking place with few, if any, checks and balances. So even though a person shows no signs of cancer, palpable or microscopic, the regulatory networks that protect that individual's cells may be ailing. And when those networks become diseased, the door for cancer is opened. It may take years for a tumor to actually develop and metastasize, but once it does, the avalanche has begun.

Sure, some skiers survive avalanches, just as some patients survive invasive cancers. But, argues Sporn, doesn't it make more sense not to allow the triggering conditions to form in the first place? For more than 30 years, he has been making the case that prevention and preemption offer the only real hope for winning the war on cancer—a war that he and others say we are losing.

In this conference hall, Sporn is preaching to the already converted. His talk is one of dozens at the annual cancer prevention research conference of the American Association for Cancer Research (AACR).

Michael Sporn, who coined the term "chemoprevention," has been at Dartmouth since 1995.

It's a relatively small AACR conference, with about 900 attendees. (The organization's annual meeting, for example, draws about 17,000 people.) Sporn is a heroic figure to many of the attendees. "An inspiration," "a genius," "a prophet" is how they refer to him during other presentations and in one-on-one conversations.

But his lecture is more than motivational; it contains arguably the most exciting data presented at the four-day conference. Sporn and his

Now he drives his metaphor home, asking, "What is a healthy
person?" Is someone who
shows no outward signs of disease necessarily healthy?
"No," argues Sporn.

collaborators—Dartmouth organic chemists Gordon Gribble and Tadashi Honda—have synthesized several compounds that not only shrink existing tumors but also prevent them—with few,

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Jennifer Durgin is Dartmouth Medicine's senior writer.

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