Stephen D. Hursting, PhD, MPH

2007-2008 BCRF Project:
The prevalence of obesity, an established risk factor for breast cancer in postmenopausal women, has risen steadily for the past several decades in the US. Unfortunately, the mechanisms underlying the association between obesity and cancer are not well understood, hampering the development of strategies to offset the negative effects of excess weight on cancer risk. It is widely believed that the obesity-cancer link is primarily influenced by the increased fat accumulation that accompanies obesity, particularly through excess secretion of substances from the fat, such as adipokines.

However, Dr. Hursting's recent findings from BCRF-funded work (that has resulted in nine papers published or in press and four submitted in the past 12 months) suggest the hypothesis that insulin resistance (a common precursor of diabetes) and inflammation, rather than adipose tissue per se or the secreted factors produced by fat cells, are the key targets for disrupting the obesity-cancer link. This is the current focus of his BCRF-funded research program, which has already established that obesity (in the absence of ovarian hormones, mimicking the postmenopausal state) enhances mammary tumor development. In contrast, preventing obesity by a low-calorie diet suppresses mammary tumor development, regardless of ovarian hormone status.

The researchers have also completed microarray studies, as well as studies in fatless/diabetic models and models lacking insulin-like growth factor-1, all suggesting that pathways related to inflammation and the insulin/insulin-like growth factor pathway are altered by energy balance interventions such as diet-induced obesity, low calorie diets and exercise. Dr. Hursting and his team are working to complete these studies with the goal of identifying strategies for reversing the breast tumor enhancing effects of obesity.

Mid-Year Progress Report:
The specific mechanisms by which obesity affects breast cancer outcome are not clearly understood. One potential mechanism may be through alteration of tumor sensitivity to hormone therapy (such as Tamoxifen, aromatase inhibitors or Faslodex). Unfortunately, the interactions between endocrine therapies, obesity, and breast cancer have not been well studied.

Dr. Hursting's previous BCRF-funded work has led him to hypothesize that the obesity-induced increases in insulin and IGF-1 levels activate a key survival pathway (called Akt) in tumor cells, resulting in decreased sensitivity to many forms of endocrine therapy. He and his team are testing this hypothesis in a novel model of postmenopausal breast cancer. They have completed an initial study, which indicates that Rad 001, a specific inhibitor of the resistance-related pathway, effectively suppresses tumor development by itself, and increases the anticancer response to the aromatase inhibitor letrozole. They are also characterizing the effects of these interventions on hormone and growth factor levels and steady state signaling in the normal mammary gland and mammary tumors.

Results from these studies will facilitate the development of novel prevention and treatment strategies for offsetting the effects of obesity on postmenopausal breast cancer, with a focus on the role of the insulin-like growth factor/Akt/mTOR pathway in endocrine therapy resistance. Successful accomplishment of the proposed aims will provide a strong foundation for future translational studies, including a planned intervention study in postmenopausal women in collaboration with BCRF grantee Dr. Electra Paskett at Ohio 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.