Cutting Copper to Combat Cancer

Reducing copper in the body fights tumor growth

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HealthDay Reporter

FRIDAY, Sept. 13, 2002 (HealthDayNews) -- Researchers at the University of Michigan have unraveled some of the cellular mechanisms that explain why a particular drug is able to slow the growth of some cancerous tumors.

The drug, tetrathiomolybdate or TM, was originally developed to reduce excess copper levels in patients with Wilson's disease, a rare and potentially lethal genetic disorder.

Scientists had noticed in other research that blood vessels didn't grow well when copper levels were depleted.

Dr. Sofia D. Merajver, senior author of the study appearing in the current issue of Cancer Research, and her colleagues wondered if using the drug to lower copper levels in cancer patients would reduce the uncontrolled growth of blood vessels that fuel tumors.

"We surmised that perhaps the copper requirement for angiogenesis was higher than for very fundamental single cell processes that depend on copper," says Merajver, an associate professor of internal medicine and director of the University of Michigan Breast and Ovarian Cancer Risk Evaluation Program.

Angiogenesis refers to the growth of blood vessels, a normal and essential process. Uncontrolled angiogenesis, however, is an important factor contributing to the growth of cancerous tumors.

When the researchers gave TM to mice that had been programmed to develop cancer, no cancer growths appeared. In fact, lab mice given TM on a regular and long-term basis thrived, though their mammary glands harbored tiny cancers that were not acquiring blood vessels.

The next -- giant -- step was to see what would happen in humans.

"Nobody had intentionally made humans copper deficient. This wasn't a joke," Merajver says. "Here we were taking people walking and talking. It was not completely obvious that this was an OK thing to do."

But it soon became obvious. In 1997, Merajver opened clinical trials involving humans with end-stage cancer, people who had exhausted all other options. Among 42 patients, almost half (45 percent) experienced stabilization or some regression of their disease, an effect that lasted for six months or more. This was among a group of patients with a typical life expectancy of about three months. One patient from that trial is still alive and has been on TM for four years.

Throughout the last six years of research, Merajver and her colleagues have been searching for the magic "why." Why do low copper levels have this effect on tumors?

As it turns out, the explanation is deceptively simple. A master switch that controls many different molecules that promote angiogenesis and inflammation is inhibited by a copper deficient environment.

"It's a very efficient way to turn things off," Merajver explains. "It's a brand new concept that copper plays any role at all in the master switch. This was completely unknown."

The drug is unlikely to play a role in advanced cancer but could be promising for early stage cancer, she says.

"We are very excited about the practical applications and we are also very excited about perhaps opening the door to new avenues of basic science investigation," says Merajver.

While the findings may be cause for quiet celebration, experts caution that the results are extremely preliminary.

"It's obviously very interesting. But I think one of the problems is that [people develop] great expectations and, unfortunately, in the world of angiogenesis, there has been a lot of tremendous enthusiasm with very little proof that any of the agents have an effect in terms of the clinical care of patients," says Dr. Jay Brooks, chief of hematology/oncology at the Ochsner Clinic Foundation in Baton Rouge, La.

"That does not mean that this research should not go on but to actually translate this into clinical practice will take time," he says.

What To Do

For more information on the field of angiogenesis, visit the Angiogenesis Foundation, or the Angiogenesis Research Center.

SOURCES: Jay Brooks, M.D., chief, hematology/oncology, Ochsner Clinic Foundation, Baton Rouge, La.; Sofia D. Merajver, M.D., Ph.D., associate professor of internal medicine and director of the University of Michigan Breast and Ovarian Cancer Risk Evaluation Program, Ann Arbor; Sept. 1, 2002 Cancer Research

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