Stephen D. Hursting, PhD, MPH
Professor and McKean-Love Chair of Nutrition, Cellular and Molecular Sciences
The University of Texas
2013-2014 BCRF Project:
(The ANN INC. Award)
Dr. Hursting’s overarching purpose is to develop prevention strategies which will favorably impact overall health without reducing quality of life. Excess breast cancer risk associated with obesity is thought to be caused by chronic inflammation resulting in an excess of inflammatory cell (macrophage) infiltration into breast and other fat. This in turn results in an imbalance of fat hormones called adipokines, inflammatory mediators called cytokines, increases in insulin, estradiol and testosterone, and increases in ductal cell proliferation and abnormal cell survival, all risk biomarkers for breast cancer. It is important to decipher these complex signals that are involved in the link between obesity and breast cancer and to use that information to design safe and effective strategies for breast cancer prevention.
For the past four years, Dr. Hursting’s team at the University of Texas has combined their expertise in obesity, metabolism and laboratory models of breast cancer with a team of breast cancer prevention trialists, led by fellow BCRF grantee Dr. Carol Fabian at the Kansas University Medical Center, to better integrate basic laboratory studies and clinical trials. The goal of this multidisciplinary collaboration is to accelerate progress in translational cancer prevention research. Their recent work has focused on the marine omega-3 fatty acids EPA and DHA’s. Their ability to resolve chronic inflammation makes them ideal partners with weight loss both for general health as well as breast cancer risk reduction. The mechanism by which EPA and DHA reduce inflammation is not completely clear but may involve a decrease in macrophage infiltration into breast fat and decreased production of inflammatory mediators called cytokines. The researchers have previously shown in BCRF-funded studies that obesity stimulates the growth of several molecular subtypes of breast cancer, particularly luminal A and basal-like subtypes (including claudin-low breast cancers, one of the most dangerous forms of the disease). To better understand the mechanisms of EPA and DHA, particularly in relation to obesity, they completed studies of the effects and mechanisms of Lovaza (a pharmaceutical-grade formulation of EPA and DHA) on mammary cancer growth in lean and obese laboratory models. Lovaza had no effect on body weight but reversed obesity-related metabolic problems and decreased (by ~50%) the growth of basal-like and (importantly) claudin-low breast cancers (a very deadly subtype) in obese models. These findings were presented at the 2013 Experimental Biology Annual Meeting. More recently, a new twist on the inflammatory story emerged with the researchers’ recent finding that Lovaza offsets the effects of obesity on the levels of several prostaglandins (eg, PGE2 and E3), and other inflammatory lipid metabolites that represent new targets for breast cancer prevention. A manuscript reporting this work is nearing submission.
Dr. Hursting’s group has also completed a series of cellular studies of Lovaza effects in several human breast cancer cell lines reflecting the major intrinsic molecular subtypes of human breast cancer. Lovaza suppressed cell growth and survival in all subtypes of breast cancer with the exception of HER2- overexpressing breast cancer cells. Thus, Lovaza may be viable as an anti-cancer agent in luminal A, luminal B and basal-like subtypes but not HER2 overexpressing breast tumor cells. A paper on this work is nearing submission, and the researchers are currently testing the ability of Lovaza to reverse the adverse effects of obesity in a genetic model of basal-like breast cancer. Basal-like breast cancers are typically referred to as triple negative breast cancer because they often lack estrogen or progesterone receptors and Her2; currently there is nothing in the existing arsenal of drugs to prevent these types of cancers, as hormonal agents like aromatase inhibitors primarily only work when hormone receptors are present. Thus, if Lovaza is found to be effective against basal-like/triple negative breast cancer, that would be an important contribution. The researchers are also following up in the current spontaneous tumor studies their previous BCRF-funded findings that microRNAs regulate several key pathways that respond to both obesity and marine fish oils.
Dr. Hursting published 15 papers citing BCRF support in 2012-2013, and was invited to discuss BCRF-funded studies at seven international meetings and ten national meetings and 14 universities in the US.
Dr. Stephen D. Hursting is Professor and Chair of the Department of Nutritional Sciences, as well as the Margaret McKean-Love Chair of Nutritional, Molecular and Cellular Sciences, at the University of Texas at Austin. He is also Professor of Carcinogenesis at the UT-MD Anderson Cancer Center. Dr. Hursting earned his PhD in nutritional biochemistry and MPH in nutritional epidemiology from the University of North Carolina at Chapel Hill, and he completed postdoctoral training in molecular carcinogenesis and cancer prevention as a Cancer Prevention Fellow at the NCI. Prior to joining the University of Texas faculty, Dr. Hursting was Chief of the NCI's Nutrition and Molecular Carcinogenesis Laboratory Section and Deputy Director of the NCI's Office of Preventive Oncology (1999-2005).
Dr. Hursting's research interests center on diet-gene interactions relevant to cancer prevention, particularly the molecular and hormonal mechanisms underlying energy balance-breast cancer associations. His research program, which has resulted in more than 125 peer-reviewed publications, focuses on three interrelated areas: 1. mechanism-based nutrition and cancer prevention studies in genetically engineered mice; 2) molecular and metabolic mechanisms underlying the energy balance and carcinogenesis relationship, with a particular interest in the roles of the IGF-1/Akt/mTOR signaling pathways and inflammatory pathways in breast and pancreatic cancers; and 3) translational nutrition and chemoprevention studies linking preclinical research with complementary clinical or epidemiologic studies.