The molecular mechanisms of exercise in cancer prevention and management.

Physical activity plays a crucial role in cancer prevention and management, reducing the risk of colorectal, breast, lung, bladder, and gastric cancers by 10-20%. In patients with cancer, regular exercise not only alleviates treatment-related side effects such as fatigue, nausea, and muscle loss but also enhances overall survival, with studies showing a 40-50% reduction in cancer-specific mortality, particularly in breast, colorectal, and prostate cancers. These benefits are achieved through multiple biological mechanisms. Exercise modulates inflammation by reducing proinflammatory cytokines and inhibiting nuclear factor kappa B signaling, enhances antitumor immunity via activation of natural killer cells and CD8 + T lymphocytes, and improves metabolic regulation by increasing insulin sensitivity and lowering circulating insulin and insulin-like growth factor-1 levels. It also inhibits key oncogenic pathways, such as the phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin axis, which is crucial for tumor growth and survival. Additionally, exercise supports genomic stability by upregulating DNA repair enzymes and further strengthens antitumor immunity, potentially promoting M1 macrophage polarization and limiting immune evasion by tumors. These mechanisms may also synergize with immunotherapies, including immune checkpoint inhibitors, to improve treatment responses. Despite strong evidence supporting the beneficial effects of exercise in oncology, further research is needed to determine optimal exercise types, intensities, and timing, as well as their interactions with emerging therapies. This review will explore the role of exercise in cancer prevention and treatment, emphasizing its molecular mechanisms to improve clinical outcomes based on current evidence.