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Stephen D. Hursting, PhD, MPH
Professor, Department of Nutrition
Nutrition Research Institute and
Lineberger Comprehensive Cancer Center
University of North Carolina
Chapel Hill, North Carolina
Goal: To understand the drivers of obesity-related breast cancer and develop effective prevention interventions.
Impact: Dr. Hursting is conducting studies to determine if the obesity-associated risk of breast cancer can be reversed using a combination of dietary interventions and medication. This strategy may be a more affordable and feasible alternative to other weight-loss strategies that can reduce breast cancer risk, including bariatric surgery and severe diet restriction.
What’s next: Dr. Hursting will examine whether an intermittent low-calorie diet induces the healthy changes in the gut microbiota achieved by the more severe diet or expensive surgical interventions.
Being overweight or obese is known to increase the risk of several types of cancer, including breast cancer. Combining bariatric surgery with a severe calorie-restricted diet is an effective way to lose large amounts of weight—and thus may also reduce the risk of breast cancer—but the former is expensive and can be risky, and the latter is difficult for people to maintain. Dr. Hursting is conducting studies to identify methods to mimic the anti-cancer effects of these approaches via less extreme dietary interventions, and anti-inflammatory medication.
Full Research Summary
Research area: Identifying ways to mimic the anti-cancer effects experienced by obese people who undergo bariatric surgery.
Impact: Obesity is an important risk and prognostic factor for several types of breast cancer, but a major gap in the field is whether the pro-cancer effects of chronic obesity can be reversed. Dr. Hursting has established that robust weight loss accomplished by bariatric surgery and various calorie-restricted diets fully reverses obesity-associated metabolic, inflammatory, and pro-cancer effects. Given the expense and morbidity associated with bariatric surgery, and the challenge in maintaining severe calorie restricted diets, his team compared surgical weight loss with an easily adopted intermittent energy restricted diet regimen. They found this diet to be more effective and sustainable than weight loss surgery for reversing the adverse effects of obesity on breast cancer.
Current investigation: Dr. Hursting and his colleagues are examining the relationship between reprogramming of the gut microbiome and the anticancer effects of weight loss interventions.
What he’s learned so far: Dr. Hursting found that the intermittent calorie-restriction diet, referred to as the 5-2 diet (2 days a week of a very low carbohydrate intake and 5 days of a healthy diet), reverses many obesity-induced metabolic changes. Furthermore, the 5-2 diet and supplementation with sulindac (an anti-inflammatory drug) each partially reversed the effects of obesity on inflammation, metabolic dysregulation, and mammary tumors. However, combining sulindac with the 5-2 diet failed to mimic bariatric surgery. His team also showed that the intermittent diet reprogrammed the gut microbiome (the bacteria in our intestines) to be healthier and produce fewer inflammatory metabolites.
What’s next: He and his colleagues will extend their studies to determine if the healthy changes in the gut microbiome are responsible for the breast cancer-inhibiting effects of weight loss surgery and intermittent energy restricted diet. The results of these studies could provide a new mechanistic target and intervention strategy to test in translational studies, with the goal of personalizing and optimizing dietary approaches to effectively reduce the burden of obesity-associated breast cancer.
Dr. Stephen Hursting is Professor in the Department of Nutrition and the Lineberger Comprehensive Cancer Center at UNC-Chapel Hill and Professor at the UNC Nutrition Research Institute in Kannapolis, NC. He earned his PhD in nutritional biochemistry and MPH in nutritional epidemiology from the UNC-Chapel Hill, and he completed postdoctoral training in molecular carcinogenesis and cancer prevention at the National Cancer Institute (NCI). Prior to joining the UNC faculty in 2014, Dr. Hursting was Professor and Chair of the Department of Nutritional Sciences at the University of Texas at Austin and Professor of Molecular Carcinogenesis at the UT-MD Anderson Cancer Center (2005-14). He also served as Deputy Director of the NCI’s Office of Preventive Oncology and Chief of the NCI’s Nutrition and Molecular Carcinogenesis Laboratory Section (1999-2005). His research interests center on diet-gene interactions relevant to cancer prevention, particularly the molecular and metabolic mechanisms underlying obesity-breast cancer associations, and the interplay between obesity, diabetes and breast cancer risk and response to therapy. Primarily using specially engineered laboratory models of breast cancer in parallel with breast cancer prevention trials (in collaboration with Dr. Carol Fabian at the Kansas Cancer Center), he is currently focusing on the molecular and metabolic changes occurring in response to lifestyle-based (dietary and physical activity), or pharmacologic manipulation of energy metabolism and cell signaling pathways, with emphasis on the IGF-1/Akt/mTOR and Wnt signaling pathways as well as inflammation. He also has expertise in assessing diet-related serum and tissue biomarkers, including hormones/growth factors, cytokines and chemokines, and microRNA’s in tissue samples.