Andrew Dannenberg, MD

2007-2008 BCRF Project:
Co-Investigator: Clifford Hudis, MD, Memorial Sloan-Kettering Cancer Center, NY

Drs. Dannenberg and Hudis are exploring the relationship between the COX enzymes (Cox-1 is present in normal tissue whereas COX-2 is increased in response to injury and abnormal growth) and cancer. They have shown that the prostaglandin products of COX enzymes increase formation of proteins including aromatase (the enzyme that makes estrogen). This female hormone can drive breast cancer formation and growth. and thereby suppress estrogen synthesis. Because widely available anti-inflammatory drugs inhibit COX enzymes and therefore may lower estrogen level, this work can explain the potential reduction in breast cancer among regular aspirin uses and expand on the use of this kind of cancer prevention approach.

COX enzymes generate prostaglandin products through a series of steps that can be inhibited. The researchers ongoing work is aimed at identifying new components of this system, including prostaglandin receptors that can be targeted with medications to both prevent and treat breast cancer. Over the past several months, Drs. Dannenberg and Hudis have found that a specific subset of prostaglandin receptors is critical for inducing aromatase (and therefore estrogen production), and they have identified more completely the mechanism by which these receptors exert their effects. Ultimately, this understanding should help to identify better and safer methods of preventing and treating breast cancer. Over the next year, they will work to further elucidate the role of COX-derived prostaglandins in breast cancer, towards a goal of improved preventive strategies.

Mid-Year Progress Report:
Since the beginning of the grant year, the researchers have further described the impact of prostaglandin signaling on the activity of the breast cancer gene, BRCA1, and its impact on aromatase activity and therefore estrogen production. This increased understanding of prostaglandins and BRCA1 should help to identify better and safer methods of treating and preventing breast cancer. A related paper was published in The Journal of Biological Chemistry in December 2007.

Bio:
Andrew J. Dannenberg, MD, is Director of Cancer Prevention at New York Presbyterian Hospital-Cornell. He is also the Henry R. Erle, M.D.-Roberts Family Professor of Medicine at Weill Medical College of Cornell University. Dr. Dannenberg received his medical degree from Washington University in St. Louis and served as a medical resident and fellow at The New York Hospital-Cornell Medical Center. He is a member of the American Society for Clinical Investigation, the American Association for Cancer Research, American Gastroenterological Association, American Association for the Study of Liver Diseases, and the International Society of Cancer Chemoprevention.

Among the honors and awards received by Dr. Dannenberg are the Upjohn Achievement Award for scientific research, the American Liver Foundation Scholar Award and the International Life Sciences Research Foundation Award. He is a member of Alpha Omega Alpha and Phi Beta Kappa. Dr. Dannenberg has authored more than 100 scientific articles, as well as edited several books and journals, including COX-2: A New Target for Cancer Prevention and Treatment.