Breast cancer is the most common cancer among women worldwide and is a leading cause of death from cancer in women. In addition, since a number of effective treatments exist for breast cancer, this represents by far the most prevalent cancer in the world, with more than 5 million women currently living with this disease. Although death from breast cancer is most commonly due to recurrence of the disease, little is known about the mechanisms that underlie relapse. Dr. Lewis A. Chodosh from the University of Pennsylvania School of Medicine in Philadelphia led a study using a mouse model of recurrent breast cancer to examine the mechanisms that allow tumors to evade therapy and reappear after a disease-free interval.
The researchers show that recurrent mammary tumors in the mouse model display characteristics of a cellular transition that was previously linked with breast cancer and also exhibit increased levels of the transcriptional repressor, Snail. Snail was sufficient to induce this cellular transition in primary breast cancer cells and to promote mammary tumor recurrence in mice. Further, genetic screening of human breast cancer samples revealed that high levels of Snail expression strongly predicted decreased relapse-free survival in women with breast cancer.
This study reveals one of the first molecular pathways to be causally implicated in mammary tumor recurrence, and suggests that Snail may play a role in the progression of human breast cancers. "While it is not possible to confirm a causal role for Snail in human breast cancer recurrence until drugs are available to inhibit this pathway, we believe that treatment of patients with pharmacologic agents that block Snail expression or function may be a promising approach to preventing breast cancer relapse. Snail may thereby represent an important target for a new generation of cancer therapeutics directed against specific molecules involved in breast cancer recurrence," explains Dr. Chodosh.
The researchers include Susan E. Moody, Denise Perez, Tien-chi Pan, Christopher J. Sarkisian, Carla P. Portocarrero, Christopher J. Sterner, Kathleen L. Notorfrancesco, and Lewis A. Chodosh of the University of Pennsylvania School of Medicine inPhiladelphia, Pennsylvania; and Robert D. Cardiff of the University of California, Davis in Davis, California. This work was supported in part by NIH grants CA92910, CA93719, CA98371, and CA105490 from the National Cancer Institute, and by U.S. Army Breast Cancer Research Program grants DAMD17-02-1-0728 and W81XWH-04-1-0353.
Moody et al.: "The Transcriptional Repressor, Snail, Promotes Mammary Tumor Recurrence" Publishing in Cancer Cell, Vol. 8, September 2005, pages 197-209. DOI 10.1016/j.ccr.2005.07.009 www.cancercell.org
Journal
Cancer Cell