Scientists Find Drug To Shrink Tumors

Harvard Medical School researchers are cautiously optimistic about a new drug that shrinks and blocks the growth of cancer tumors in mice.

While the promising new drug, endostatin, has yet to be tested in humans, it has successfully starved tumors into submission by preventing their access to the blood vessels in mice. The vessels carry oxygen-rich blood, essential for all body tissue to survive.

The drug is a protein naturally present in the bodies of both mice and humans, giving scientists hope that the drug may one day be used to treat cancer patients.

However, Dr. Michael S. O'Reilly, research fellow in surgery and the drug's discoverer, emphasized that the mouse tests are in their preliminary phases and that "succeeding in mice is tentative at best."

But so far, there is definite cause for encouragement. "We haven't found any [type of] cancer that doesn't respond," O'Reilly added.

The results of the mice experiments were published two weeks ago in the prestigious scientific journal Cell.

The discovery of endostatin is significant because the drug can potentially be targeted at all forms of cancer tumors.

Tumors behave differently in different parts of the body. Traditionally, many other cancer drugs have been effective in treating only particular kinds of tumors.

Since every tumor depends on a blood supply to live, they are all potentially vulnerable to drugs like endostatin.

"They all should be susceptible," O'Reilly said.

O'Reilly's studies have shown that colon, breast and prostate cancers have all been successfully treated with endostatin.

The search for the drug began in the 1970s, when Dr. Judah Folkman, now Andrus professor of pediatric surgery at the Medical School, postulated that tumors, like other body tissue, were dependent upon blood supply to grow.

At that time, his thinking was criticized quite stridently by colleagues.

But his later studies, and those of his assistants like O'Reilly, have made a mockery of the criticism, while expanding treatment possibilities for patients.

O'Reilly discovered two proteins--endostatin and a similar, previously identified protein called angiostatin--in his efforts to test Folkman's hypothesis.

Folkman hypothesized that large, primary tumors secrete an inhibitory substance to prevent blood vessel formation and the growth of the many smaller, secondary tumors that coexist in diseased individuals.

The critical point in O'Reilly's research came when he discovered that what inhibits the tumor growth is a collection of proteins produced by the body itself.

O'Reilly said that purifying the proteins was quite a chore.

"We had two hundred liters of mouse urine, collected by yours truly," he said.

O'Reilly explained that endostatin and angiostatin--a similar protein still being studied as well--both are part of larger complexes in the body.

Endostatin is part of the molecule collagen 18, while angiostatin is part of plasminogen, a blood clotting agent.

It is likely that these proteins lead a double life, mainly functioning in the large complexes but also naturally acting as cancer fighters.

"Most people have microscopic cancers in their bodies," O'Reilly said. "Autopsies of men who died of other causes reveal that 90 to 100 percent of them had cancers in their prostates."

It is possible that the inhibitor proteins function to control these small cancers in all individuals, and that their use in large doses could mimic the body's natural defenses, albeit on a larger scale.

Future research may enable scientists to turn on these cancer-fighting genes so the proteins are produced at high levels by the body. Without any pills, needles or chemotherapy, the body itself could produce weapons to fight the disease.

For now, O'Reilly pictures the drug as one piece of artillery in a larger arsenal that includes chemotherapy and other drugs.

Like Folkman, O'Reilly has a surgery background and does clinical work in addition to his research.

He said that the combination has been a factor in the success of the research.

"Every day I see people who need stuff like what I'm working on," O'Reilly said. "It really emphasizes why I'm doing the research.

O'Reilly said that purifying the proteins was quite a chore.

"We had two hundred liters of mouse urine, collected by yours truly," he said.

O'Reilly explained that endostatin and angiostatin--a similar protein still being studied as well--both are part of larger complexes in the body.

Endostatin is part of the molecule collagen 18, while angiostatin is part of plasminogen, a blood clotting agent.

It is likely that these proteins lead a double life, mainly functioning in the large complexes but also naturally acting as cancer fighters.

"Most people have microscopic cancers in their bodies," O'Reilly said. "Autopsies of men who died of other causes reveal that 90 to 100 percent of them had cancers in their prostates."

It is possible that the inhibitor proteins function to control these small cancers in all individuals, and that their use in large doses could mimic the body's natural defenses, albeit on a larger scale.

Future research may enable scientists to turn on these cancer-fighting genes so the proteins are produced at high levels by the body. Without any pills, needles or chemotherapy, the body itself could produce weapons to fight the disease.

For now, O'Reilly pictures the drug as one piece of artillery in a larger arsenal that includes chemotherapy and other drugs.

Like Folkman, O'Reilly has a surgery background and does clinical work in addition to his research.

He said that the combination has been a factor in the success of the research.

"Every day I see people who need stuff like what I'm working on," O'Reilly said. "It really emphasizes why I'm doing the research.