Increasing worldwide cancer incidence coupled with spiralling treatment costs highlights the need for novel preventive strategies. Therapeutic prevention is increasingly seen as a cost-effective approach to reducing cancer incidence and mortality. Diet-derived compounds are attractive candidates for the prevention of cancer in healthy high-risk populations, with those that are consumed regularly by humans likely to have a good safety profile. However, translating promising epidemiology and/or preclinical data to randomised controlled trials to assess clinical efficacy is challenging, as is the conduct of such trials. This presentation will outline these challenges, and describe how they can be navigated, using resveratrol as an exemplar phytochemical, which we have taken from bench to the bedside, culminating in the ongoing COLO-PREVENT polyp prevention trial, a world first trial platform for assessing colorectal cancer preventive therapies.
 
 
COLO-PREVENT is testing resveratrol, alongside the well-established drugs aspirin and metformin in high-risk patients identified through the NHS Bowel Cancer Screening Programme. It consists of a phase 2 signal seeking trial in which two doses of resveratrol, a low dietary achievable dose (5 mg daily) and high pharmacological dose (1 g), are being compared against placebo, and a parallel phase 3 trial assessing aspirin alone versus a combination of aspirin plus metformin, with polyp number as the primary endpoint. The trial is currently open, and will be conducted across 60 sites within all four nations of the UK. As of January 2026, 57 participants have been recruited to the resveratrol study, with 212 randomised to the aspirin and metformin trial; the final targets are 477 and 862 patients, respectively.  COLO-PREVENT also includes a large embedded translational programme focussed on precision prevention, with the aim of identifying predictive and pharmacodynamic biomarkers that can ultimately be used to select the optimum therapy for each individual and monitor efficacy. Areas of focus include examining how metabolic status and the gut microbiome, characterised at baseline and over the course of the trial may influence the efficacy of each preventive therapy as well as elucidating the underlying mechanisms.