Physical exercise as an adjunctive therapy in obesity-associated cancer: From biological rationale to a pragmatic clinical framework

: Obesity represents a well-established risk factor for numerous cancers, contributing substantially to the global burden of this disease. In parallel, accumulating evidence supports the relevant biological effects of physical activity in counteracting the pathological mechanisms linking obesity to carcinogenesis and tumor progression, including chronic low-grade inflammation, adipocyte dysfunction, and insulin resistance, which collectively promote the establishment of a pro-tumorigenic microenvironment. Despite the growing body of evidence on the benefits of physical activity in oncological patients, its translation into practical recommendations for individuals with both obesity and cancer remains limited, representing a critical clinical and scientific gap. The present review aims to provide a critical overview of the biological basis and available evidence, with the goal of proposing a pragmatic evidence-informed clinical framework for the integration and prescription of physical exercise in the management of patients with cancer and obesity. Major international guidelines on physical activity in oncology will be analyzed, highlighting areas of convergence and operational gaps, with particular emphasis on the absence of specific recommendations for this dual pathological condition. Exercise modality, dose, progression, and timing will be discussed, with attention to the most relevant individual and systemic barriers. Collectively, the available evidence supports the integration of individualized exercise prescription as a core component of multidisciplinary care for patients with obesity-associated cancer, while highlighting the urgent need for dedicated clinical trials and consensus recommendations specifically addressing this high-risk population.