Researchers awarded nearly $2M to investigate GLP-1 medicines for the prevention of obesity-related cancers

“Obesity and related metabolic dysfunction is a global epidemic, and it’s going to become one of the leading causes of cancer. This study lays the foundational work to help us understand the biology of GLP-1 medicines and its potential impact on cancer,” said Dr. Hung, who holds the Canada Research Chair in Integrative Molecular Epidemiology and is also the Associate Director of Population Health and Head of the Prosserman Centre for Population Health Research at LTRI. “By addressing the metabolic dysfunction associated with obesity, we hope to reduce the cancer burden globally.” 

Obesity and its associated metabolic dysfunction—driven by excess accumulation of visceral, or adipose, fat around vital organs—  are known to increase the risk of at least 13 different cancers. By 2042, cancer cases in Canada attributable to adiposity-related metabolic issues are expected to nearly triple, making obesity the second most preventable cause of cancer after tobacco. 
GLP-1 drugs, such as semaglutide, have already transformed the treatment of diabetes and obesity with demonstrated benefits extending to heart, liver, and kidney disease. Emerging evidence suggests these medicines may also reduce cancer risk through two mechanisms: weight loss and reduction of chronic inflammation, independent of weight loss. 

The broad anti-inflammatory effects of GLP-1 medicines that occur independently of weight loss have been demonstrated in preclinical models by Dr. Daniel Drucker, a senior investigator at LTRI and co-investigator on the project. Last year, Dr. Drucker, was recognized with the Breakthrough Prize for his pioneering work that has enabled today’s GLP-1 therapies.

In addition to GLP-1 medicines, the team will also investigate other weight loss strategies, based on individual metabolic profiles. The study will focus on pancreatic and post-menopausal breast cancer, both of which are adiposity-related cancers with a high disease burden in the population.
The PROBE project, which stands for Prevention of Adiposity-related Cancers via Biology and Evidence Triangulation, brings together three complementary lines of inquiry to better understand how obesity interventions may reduce cancer risk. In laboratory studies, researchers will use preclinical models to examine how GLP-1 medicines influence tumour growth through both weight loss-dependent and weight loss-independent mechanisms.

In parallel, circulating protein biomarkers from human blood samples will be analyzed before and after different adiposity interventions including GLP-1 medicines, exercise and bariatric surgery, to reveal how these interventions modulate cancer-related pathways. The team will also draw on large population cohorts from Canada, Europe and the United Kingdom to build and validate a biology-informed predictive model for pancreatic and post-menopausal breast cancer that incorporates individual metabolic health and risk profiles. Together, these approaches aim to guide a personalized obesity-intervention strategy that can reduce cancer risk.  

“If GLP-1 turns out to reduce rates of cancer or improve cancer survival, even in the absence of weight loss, that opens the door to a much more accessible therapeutic option than bariatric surgery,” Dr. Drucker said, highlighting that exercise and a healthy diet remain critical for cancer prevention.

Rounding out the team are experts whose clinical and scientific expertise strengthen every dimension of the project, including LTRI’s Dr. Ravi Retnakaran, a clinician scientist and endocrinologist specializing in diabetes and metabolism and Dr. Kieran Campbell, an investigator focusing on computational biology of cancer; and Dr. Sabrina Kolker, a family medicine physician at Sinai Health.
The Sinai Health team will also work with national and international collaborators including Dr. Jennifer Brooks, Director of CanPath, Canada’s largest population study, Dr. Christine Friedenreich, at the University of Calgary, an expert on the role of exercise for cancer prevention, Dr. Marc Gunter, obesity and cancer epidemiologist at the Imperial College London, UK, Dr. Ian Patton and Dr. Sanjeev Sockalingam representing Obesity Canada, and Dr. Craig Earle, CEO of Canadian Partnership Against Cancer.