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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

Current Research

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: He and his team will study a weight-loss approach that combines a diet intervention, exercise, and treatment with the aspirin-like anti-inflammatory drug sulindac to see if it mimics the reduction in breast cancer risk seen in those who undergo bariatric surgery and follow severe calorie-restricted diets.

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 that approach via a combination of exercise, 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. Weight loss could potentially reverse this risk. Dr. Hursting’s BCRF-supported studies suggest that moderate weight loss may not be enough to reverse the cancer-associated metabolic and inflammatory perturbations that occur with chronic obesity. The more severe weight loss that follows bariatric surgery (combined with severe calorie-restricted diets) does correct these perturbations and prevents the development and growth of mammary tumors in an experimental model of basal-like breast cancer. 

Such an approach does have downsides. Bariatric surgery is expensive and comes with serious risks, and very low-calorie diets are difficult to maintain. Dr. Hursting is investigating other weight-loss interventions that may yield the same anti-cancer effects, thereby reducing the risk of breast cancer.

Current investigation: He and his team have been studying a combination of an intermittent energy-restricted diet (shown to be more effective and sustainable than a low-fat diet or a constant energy-restricted diet) with the aspirin-like anti-inflammatory drug sulindac. The intermittent calorie-restriction diet involves 2 days a week of a very low carbohydrate intake and 5 days of a healthy diet (referred to as the 5-2 diet) and reverses many obesity-induced metabolic changes.

What he’s learned so far: Dr. Hursting found that the 5-2 diet and sulindac supplementation each partially reversed the effects of obesity on inflammation, metabolic dysregulation, and mammary tumors. Combining the sulindac with the 5-2 diet failed to mimic bariatric surgery, however. Further study revealed that obesity drives immunosuppression in the tumor microenvironment that is only partially reversed by sulindac and minimally impacted by the 5-2 diet. 

What’s next: He and his colleagues will extend their studies by adding an exercise arm to the sulindac and/or 5-2 diet regimen.

Biography

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.

Grid Researcher Headshot - Hursting S

BCRF Investigator Since

2003

Donor Recognition

The ANN INC. Award (a division of ascena retail group inc.)