Clifford Hudis, MD
Chief, Breast Cancer Medicine Service and Attending Physician
Memorial Sloan-Kettering Cancer Center, New York, NY
Chairman, BCRF Scientific Advisory Committee
Co-Investigator:
Andrew Dannenberg, MD, Weill Medical College of Cornell University, NY
Drs. Hudis and Dannenberg 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:
Dr. Hudis is Chief of the Breast Cancer Medicine Service and Attending Physician at Memorial Sloan-Kettering Cancer Center in New York City. He is also a Professor of Medicine at the Weill Medical College of Cornell University. In 2007, Dr. Hudis was appointed as chairman of The Breast Cancer Research Foundation’s Scientific Advisory Committee. He is co-leader of the Breast Disease Management Team at MSKCC, co-Chair of the Breast Committee of the Cancer and Leukemia Group B (CALGB), and the Chair of ASCO’s Information Technology Committee. His research interests include chemotherapy development, hormone therapy, novel targeted therapeutics, and supportive care. A particular focus has been the integration of newer agents into the treatment plan for patients with early stage disease and translational research focused on targeted therapies.
