Weill Cornell team identifies potential new drug targets against hormone-dependent breast cancer

2 receptors play key role in boosting cellular estrogen production

NEW YORK (Feb. 27, 2008) -- The identification of two cellular receptors that likely contribute to the genesis of hormone-dependent breast cancer points the way to new, highly targeted therapies against the disease, says a team led by scientists at Weill Cornell Medical College in New York City.

The finding also helps explain how daily use of medicines such as aspirin might help keep these breast tumors at bay.

"These two receptors, called EP2 and EP4, form key links in a biochemical pathway that boosts estrogen production in fat and breast cancer cells -- this, in turn, may increase a woman's risk for developing hormone receptor-positive breast cancer. Finding ways to interrupt this pathway in a manner that causes few side effects is the ultimate goal of this research," explains the study's senior author Dr. Andrew Dannenberg, director of the newly established Cancer Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, and the Henry R. Erle, M.D.–Roberts Family Professor of Medicine at Weill Cornell Medical College.

The new findings were published recently in the online edition of the Journal of Biological Chemistry.

About 75 percent of all breast malignancies are "estrogen receptor-positive," meaning that their cells carry receptors attuned to estrogen. In the presence of the hormone, these cancer cells will divide and grow. For this reason, anti-estrogen drugs such as tamoxifen and aromatase inhibitors have come to the forefront in the fight against hormone-dependent breast cancer.

"Aromatase, an enzyme, boosts the amount of estrogen made by both fat cells and breast cancer cells," explains the study's lead author, Dr. Kotha Subbaramaiah, recently appointed the Jack Fishman Associate Professor of Cancer Prevention at Weill Cornell. "Cancer researchers have for years been exploring the pathway by which aromatase is regulated. We know that if you reduce aromatase activity that you also reduce levels of cancer-causing estrogen in breast tissues."

In 2006, researchers led by Dr. Dannenberg discovered that cyclooxygenase (COX) protein-derived prostaglandin E2 (PGE2) could turn on the gene that expresses aromatase. More recently, the healthy form of the BRCA1 tumor-suppressor gene was found to quiet the aromatase gene -- performing its duty in keeping breast cancer risk low.