The link between nutrition, metabolism and obesity and cancer was the focus of several research presentations at the 2022 American Association of Cancer Research meeting this month in New Orleans. This included a symposium presentation by Stephen Hursting, PhD, MPH, UNC Lineberger Comprehensive Cancer Center member, who discussed the latest findings underscoring obesity’s impact on cancer.
“There is convincing evidence that obesity is linked to 13 or more types of cancer,” said Hursting, who is director of the UNC Nutrition Research Institute and professor in the Department of Nutrition at UNC Gillings School of Global Public Health. “The cancer research community now needs to pivot from the question of whether obesity is an important risk factor for many cancers – it is – to the question of how we can reduce the impact of chronic obesity on cancer.”
The fields of nutrition and metabolism, particularly as they relate to cancer, are burgeoning areas of research endeavor at UNC. Some of the experiments that Hursting is leading will benefit from a recent $25 million gift that is dedicated to advancing research in a rare form of breast cancer, triple-negative breast cancer, which research has shown to have a connection to obesity.
Obesity and cancer
In his presentation, Hursting discussed how intentional weight loss in obese people may reduce the risk of some cancers. This finding is based primarily on surgical weight loss studies. These studies are important as obesity is approaching 45 percent of the adult population in the U.S., with more than 10 percent of the population being severely obese with body mass indexes over 40. As a key example, a 2017 study of pancreatic, endometrial and post-menopausal breast cancers showed a link between reduction in cancer incidence and weight loss due to bariatric surgery.
To reverse factors related to obesity that promote cancer may require substantial metabolic reprogramming and may be more challenging than earlier research indicated, noted Hursting. But he believes the challenge is worth pursuing as one study demonstrated that women who lost more than 10 percent of their body weight, compared to those who lost less than 10 percent, showed favorable changes in biomarkers associated with breast cancer risk.
Exploring a different avenue of approach to obesity, Hursting said there was sufficient evidence in experimental animal models for a preventive effect of calorie restriction for many types of cancer. Caloric restriction utilizes a minimal diet needed that sustains life and strength without affecting quality of life. These types of studies have been linked to potentially longer life spans as well as reductions in new cancers compared to animals who were allowed to eat higher calorie diets. Hursting only presented findings on mice at the AACR symposium, but he noted that his research team has a collaboration with the University of Wisconsin and the National Institutes of Health that is looking at caloric restriction in humans and other research models that might give stronger evidence of a benefit for caloric restriction in humans.
Progress in this field was also highlighted in the 11 abstracts presented at the AACR meeting from researchers in Hursting’s lab, a few of which impact important types of cancer, such as:
Alyssa N. Ho reported that inhibiting nutrient-sensing metabolic pathways in combination with chemotherapy and/or inhibition of the removal of cellular waste might improve therapeutic responses in women with triple-negative breast cancer.
Meredith S. Carson reported that mice could be bred to be highly responsive to energy balance, representing a promising new way for preclinical studies to examine the interactions between diet, obesity and immunity.
Morgan E. Cody reported that a drug known as sulindac, a nonsteroidal anti-inflammatory drug (NSAID), can reverse genetic changes in obese mammary tumors and restore the immune system’s ability to search out cancer cells. Sulindac, or potentially other non-inflammatory drugs, may be able to protect against obesity-driven mammary tumor growth by altering antitumor immune function.
Elaine M. Glenny, PhD, reported that both weight loss and sulindac impeded the effects of chronic obesity on colon cancer development. Weight loss and sulindac effectively suppressed inflammation in fatty tissue but not in the tumor.
Suhas K. Etigunta reported that a substance known as HMB promotes immune surveillance in pancreatic cancer, synergizing with immunotherapy, to potentially treat a tumor.