Abstract
Evidence from conventional and Mendelian Randomisation epidemiological studies support the conclusion that obesity is causally associated with increased risk of several common cancer types. Some evidence, notably from quasi-experimental bariatric surgery studies, support the concept that sustained long-term weight loss in individuals is associated with reduction of cancer incidence, particularly in women. Yet, there are no authoritative public health policies directed specifically at large-scale weight management interventions to prevent obesity-related cancers. At least two adversities conspire against public health success: (i) awareness of the causal link between obesity and cancer risk; and (ii) lifestyle interventions are associated with only moderate weight loss that is generally not sustained long enough to result in clinically meaningful cancer prevention. However, there is now a revolution of effective pharmacotherapy for obesity, namely glucagon-like-peptide (GLP)-1 agonists and their extended family of dual and triple agonists, which leads to substantial rates of weight loss, sustained while individuals continue to take the drug. There is now a key new cancer prevention research question, whether this drug class might significantly reduce cancer risk with long-term use. The logistics of addressing this question in a clinical trial setting are discussed and potential strategies to overcome these challenges are proposed.