By Yingjie Sun, Yixiao Ma, Lei Shi, Tong Liu, Yahong Dong and Qiguan Jin
Curr. Issues Mol. Biol. 2025, 47, 374 https://doi.org/10.3390/cimb47050374
Overview
This article explores how exercise influences cancer therapy outcomes through systemic, cellular, and molecular mechanisms. Exercise is increasingly recognized as an adjunct to conventional therapies, improving physical function, mitigating treatment side effects, and enhancing survival. The review highlights key molecular pathways through which exercise impacts tumor biology, immunity, and metabolism, while also discussing translational implications for clinical oncology.
Molecular Mechanisms
Exercise exerts its effects via multiple interconnected pathways:
- Immune modulation: Physical activity enhances natural killer (NK) cell trafficking and function, improves T-cell surveillance, and reduces chronic inflammation. These changes support anti-tumor immunity and may increase sensitivity to immunotherapies.
- Metabolic regulation: Exercise improves insulin sensitivity, reduces circulating glucose and insulin-like growth factors, and decreases systemic inflammation—all linked to slower tumor progression.
- Vascular and hypoxia effects: By improving blood flow and vascularization, exercise helps normalize the tumor microenvironment, decreasing hypoxia and potentially enhancing the efficacy of chemotherapy and radiotherapy.
- Myokine release: Muscle contraction induces secretion of molecules such as IL-6, irisin, and SPARC, which exert anti-cancer effects by regulating apoptosis, proliferation, and immune activity.
- Oxidative stress balance: Regular exercise strengthens antioxidant defenses, reducing DNA damage and mutagenic potential.
Integration with Cancer Therapies
Evidence suggests that exercise synergizes with multiple treatment modalities:
- Chemotherapy: By improving circulation and tissue oxygenation, exercise can enhance drug delivery while reducing fatigue and cardiotoxicity.
- Radiotherapy: Improved tumor oxygenation augments radiosensitivity.
- Endocrine and targeted therapies: Exercise supports bone health, body composition, and metabolic control, mitigating adverse effects of long-term treatments.
- Immunotherapy: Enhanced T-cell and NK cell function may improve therapeutic response, though clinical validation is ongoing.
Clinical Implications
For clinicians, prescribing exercise should be considered an integral part of comprehensive cancer care. Guidelines recommend at least 150 minutes per week of moderate-intensity activity or 75 minutes of vigorous exercise, supplemented by resistance training. Importantly, interventions should be individualized, taking into account treatment phase, comorbidities, and patient capacity.
Exercise is not merely supportive—it may directly influence tumor biology and treatment efficacy. Clinicians should view exercise as a low-cost, evidence-based adjunct that improves both survival and quality of life. However, standardized protocols, biomarker validation, and larger randomized controlled trials remain needed to refine recommendations.
Focused Summary for Clinicians
- Exercise enhances anti-tumor immunity (via NK and T-cell activation) and reduces inflammation.
- Tumor microenvironment is favorably altered through vascular normalization and reduced hypoxia, improving chemo- and radiosensitivity.
- Metabolic benefits (improved insulin sensitivity, lower IGF-1) are associated with reduced recurrence risk.
- Myokines act as molecular mediators, linking muscle activity with cancer control.
- Clinical prescription matters: Regular, structured exercise is safe, feasible, and should be integrated into oncology practice alongside traditional therapies.
