Exercise against cancer: recent advances and open questions

More than a century after observations linking muscular activity to reduced cancer risk, exercise oncology has progressed from epidemiological association to interventional evidence. Large cohort studies associate physical activity with reduced cancer incidence and mortality, and a Phase 3 randomized trial now demonstrates cancer-specific survival benefits of structured exercise. In parallel, preclinical and emerging human studies provide mechanistic insight into how exercise may modulate tumor biology, including effects on immune surveillance, vascular function, metabolism, and systemic signaling. Despite these advances, gaps remain-notably, the limited integration of exercise variables into oncology trials and sparse mechanistic data from patients, particularly in pediatric cancers. This opinion article synthesizes recent clinical and mechanistic advances and outlines priorities for biologically informed integration of exercise into cancer research and the standard of care.