Stephen D. Hursting, PhD, MPH

2008-2009 BCRF Project:
The evidence that obesity adversely affects women's health, including increasing the risk of breast cancer in postmenopausal women, is overwhelming and indisputable. Obesity is also associated with poor prognosis of breast cancer in both pre- and postmenopausal women. The prevalence of obesity among adolescents and middle-aged women has rapidly increased over the past three decades; thus, the harmful impact of obesity on breast cancer will continue to rise as many of these women approach their postmenopausal years.

However, the specific mechanisms by which obesity affects breast cancer risk or prognosis are not clearly understood, and strategies for offsetting the negative effects of obesity are urgently needed. One potential mechanism may be through the upregulation of the Akt/mTOR signaling pathway, which has recently been associated with enhanced breast tumor development and progression and accelerated loss of responsiveness to the selective estrogen receptor modulator (SERM) tamoxifen.

Dr. Hursting and colleagues have recently reported in skin and pancreatic cancer models that diet-induced obesity, through its enhancing effects on circulating growth factors (including insulin and insulin-like growth factor (IGF)-1), upregulates Akt/mTOR signaling, and that mTOR inhibitors can at least partially offset the tumor-enhancing effects of obesity. Preliminary data in their laboratory model of ER-á-positive breast cancer suggests an interaction between obesity, mTOR signaling and the therapeutic response to tamoxifen. The objective in the current proposal is to test the hypothesis that the obesity-induced increases in insulin and IGF-1 levels activate Akt/mTOR signaling in the mammary epithelium, leading to enhanced breast cancer progression, including the transition to the ER-á-negative state.

Bio:
In association with Dr. Douglas Weed (Director, Office of Preventive Oncology), Dr. Hursting is responsible for all aspects of the NCI's Cancer Prevention Fellowship Program, a structured post-doctoral training program that provides a strong foundation for 15 to 20 new Fellows/ year to train in the field of cancer prevention and control. Dr. Hursting is also an Investigator in the NCI's Center for Cancer Research, where he heads the Nutrition and Molecular Carcinogenesis Section of the NCI's Laboratory of Biosystems and Cancer.

In collaboration with Dr. Carl Barrett (Director, NCI Center for Cancer Research) as well as colleagues at the MD Anderson Cancer Center and the National Institute of Environmental Health Sciences, Dr. Hursting's research program focuses on diet-gene interactions relevant to cancer prevention. Combining transgenic mouse model studies with molecular biology approaches, Dr. Hursting’s laboratory is determining the molecular and hormonal mechanisms underlying the energy balance-cancer association (with an emphasis on obesity and physical activity).

From 1995 to 1999, Dr. Hursting was an Assistant Professor in the Departments of Epidemiology and Carcinogenesis at the University of Texas MD Anderson Cancer, where he directed a multidisciplinary research program in nutrition and cancer prevention. He continues his affiliation with his former departments at the MD Anderson Cancer Center as an Adjunct Associate Professor.

Dr. Hursting earned a BA in biology from Earlham College and a PhD in nutritional biochemistry and an MPH in nutritional epidemiology from the University of North Carolina. Prior to joining the MD Anderson faculty, Dr. Hursting completed the NCI's Cancer Prevention Fellowship Program. He is a member of several professional organizations, including the American Association for Cancer Research and the American Society for Preventive Oncology, and is on the steering committee of NCI's Mouse Models for Cancer Prevention Faculty and the NCI's Epidemiology, Carcinogenesis and Prevention Faculty.

Dr. Hursting has published more than 150 journal articles, book chapters and abstracts, and was the recipient of the 2002 BioServ Award for Experimental Nutrition from the American Society of Nutritional Sciences, the 2002 Mentor of Merit Award from the National Cancer Institute and the 2003 Pike Award for outstanding contributions in nutrition research.