Ivana Grle, Maki Grle, Jerko Prlić, Dejan Tirić, Boženka Galić Tirić, Jasmin Budimlić, Nijaz Skender, Mate Vukoja, Boriss Bazanov, Ivica Franjko, Ahmet Naci DİLEK, Ivan Đuroci, Besnik Morina, Davor Lješević, Goran Sporiš, Patricia Zupanc, Adem Preljević, Goran Špaleta, Ernest Šabić
Exercise is increasingly positioned as an adjunct to oncology care, yet its clinical benefits and proposed antitumour mechanisms are often discussed in parallel rather than as a unified biological model. This focused mini review integrates 20 unique full-text sources spanning meta-analyses, systematic and narrative reviews, consensus guidance, and translational studies. The evidence supports a multiscale framework in which muscle contraction generates acute neuroendocrine and myokine signals, improves tumour perfusion and oxygenation, alters metabolite competition within the tumour microenvironment, mobilises cytotoxic immune cells, and preserves host muscle and functional reserve. Clinical evidence is strongest for improvements in cardiorespiratory fitness, strength, fatigue, physical function, and quality of life, whereas direct tumour control and enhancement of immunotherapy remain supported mainly by preclinical and early human mechanistic data. Important tensions include the context-dependent biology of interleukin-6, the distinction between vascular normalisation and tumour-promoting angiogenesis, the uncertain optimal exercise dose, and the risk that excessive energy expenditure may be inappropriate in severe cachexia. We propose a precision exercise oncology model that matches modality and dose to tumour phenotype, treatment phase, symptoms, physiological reserve, and dynamic monitoring. Exercise should be treated as evidence-based supportive care with plausible disease-modifying potential, not as a substitute for anticancer therapy.