Dual Drug Therapy Shows Promise Against Breast Cancer

In some cases, tumors were eradicated in mice, researchers report

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By
HealthDay Reporter

TUESDAY, Jan. 30, 2007 (HealthDay News) -- A compound designed to block growth hormone, coupled with a standard chemotherapy drug, successfully treated human breast cancer in mice.

In some cases, the tumor was destroyed.

"We inhibited a human cancer line that's not only estrogen-independent but also resistant to doxorubicin, which is a major chemotherapeutic agent for cancer treatment," said Andrew Schally, distinguished Miller professor of pathology and oncology at the University of Miami Miller School of Medicine. "Combining a growth hormone antagonist with a more modern chemotherapeutic agent, Taxol, we can virtually eradicate the disease."

Growth hormone feeds many types of tumors. Growth hormone-releasing hormone (GHRH) antagonists effectively block these growth hormones and interfere with a tumor's ability to grow.

Schally, who received the Nobel Prize in medicine in 1977, was "chased" by Hurricane Katrina to Miami from New Orleans. His former employer, Tulane University in New Orleans, has applied for a patent on the specific antagonist cited in this paper. Schally is a co-inventor on that patent.

The paper is published in this week's issue of the Proceedings of the National Academy of Sciences.

Breast cancer is the most common malignancy among women in the Western world and is the second leading cancer-killer. Once the cancer has spread, chances for recovery are slim, especially in women whose tumors are "estrogen-independent," meaning they are not reliant on the hormone estrogen to grow, Schally said.

"The treatment of estrogen-positive or estrogen-dependent breast cancer is relatively easy, because you can use tamoxifen or later compounds," he explained. "But estrogen-independent cancer is a major problem, and many women die from it."

GHRH is active in promoting many tumor types, including breast tumors.

Schally and his colleagues developed a GHRH-antagonist called JMR-132, which binds to specific receptors, preventing GHRH from helping tumor cells grow. The antagonist works locally on the tumor site and is also active against 15 other types of cancer, he said.

For this study, the researchers looked at the effectiveness of JMR-132 alone or in combination with the chemotherapy drug Docetaxel in mice that had been specially bred to develop human breast tumors.

After three weeks of treatment, the antagonist reduced tumor volume by an average of 63 percent, and Docetaxel reduced volume by 74 percent. But the combination reduced tumor volume by more than 97 percent; in some cases, the tumor was eradicated.

The combination of the two had the added advantage of few side effects.

"Chemotherapy is the most commonly used approach for therapy for those cancers that cannot be removed surgically," Schally said. "But chemotherapy has very severe side effects. It's toxic, lowers your white blood cells, red blood cells, makes your hair fall out and makes you feel miserable. This would have the major advantage of not having side effects."

But the question is whether the regimen will work in humans as well as it works in mice.

"It's an interesting study, but there's no guarantee that this would work in humans," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. "Docetaxel would work in humans, because it's the most active drug in breast cancer, but we don't know if the antagonist would work. I think this should be followed in a human clinical research trial."

Dr. Yelena Novik, assistant professor of medicine at New York University School of Medicine, added, "It's definitely preliminary, because it's animal data. The question is whether this will translate into the same response in the clinic. It's interesting, because we believe there is a future in combining traditional cancer drugs like chemotherapy drugs and newer drugs which may somehow prevent cancer cells from growing and metastasizing."

More information

For more on breast cancer, visit the American Cancer Society.

SOURCES: Andrew Schally, Ph.D., distinguished Miller professor of pathology and oncology, University of Miami Miller School of Medicine, and chief, Cancer Institute, Veterans Affairs Medical Center, Miami; Jay Brooks, M.D., chairman of hematology/oncology, Ochsner Health System, Baton Rouge, La.; Yelena Novik, M.D., assistant professor of medicine, New York University School of Medicine, and New York University Cancer Institute, New York City; Jan. 29-Feb. 2, 2007, Proceedings of the National Academy of Sciences

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