Titles and Affiliations
Professor, Department of Nutrition
Nutrition Research Institute and Lineberger Comprehensive Cancer Center
University of North Carolina
Chapel Hill, North Carolina
Research area
To understand the drivers of obesity-related breast cancer and develop effective prevention interventions.
Impact
Obesity is an important risk and prognostic factor for several types of breast cancer, but relatively few studies examine whether the cancer-promoting effects of chronic obesity can be reversed. New diabetes drugs, specifically incretin mimetics, such as glucagon-like peptide 1 (GLP-1) receptor agonists like semaglutide (Ozempic®) and tirzepatide (Mounjaro®) are highly effective and increasingly popular medications for chronic weight management and offer a particularly promising, yet understudied, option for preventing or slowing obesity-related breast cancer. However, the role of these drugs in reducing breast cancer risk remains underexplored.
Progress Thus Far
Over the past year, Dr. Hursting studied tirzepatide in both triple-negative (TNBC) and ER-positive breast cancer models and found that tirzepatide increased weight loss, improved metabolic health and immune function, and reduced tumor development. They also observed important changes in the gut microbiome with tirzepatide, particularly increased levels of the fatty acid butyrate. These findings suggest tirzepatide may hold real promise not just for treating obesity, but for intercepting the path from obesity to breast cancer. The team has since pivoted to test whether combining tirzepatide with resistance exercise can further enhance its anticancer effects while protecting against a known side effect of the drug: loss of muscle mass.
What’s next
Looking ahead, the team will take a precision prevention approach to determine how tirzepatide can reduce obesity-associated breast cancer risk, guided by three goals: establishing the drug’s cancer-preventive effects in additional preclinical models of HR-positive breast cancer and TNBC; identifying the specific genes that respond to tirzepatide and are linked to cancer prevention; and pinpointing which of these gene targets are most directly responsible for the drug’s protective effects. Together, this work aims to lay the scientific groundwork for future clinical prevention trials.
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.
