“The molecular mechanisms of exercise in cancer prevention and management”
by Jingfeng Chen, Yang Li, Li Wang and Qi Liu
Summary and Clinical Implications
This recently published review by Jingfeng Chen et al., synthesizes growing evidence that physical exercise is not merely supportive care, but a biologically active intervention capable of influencing cancer risk, progression, treatment response, and survival through well-defined molecular mechanisms
For both patients and clinicians, the article reframes exercise as a core component of modern oncology care, comparable in importance to pharmacologic adjuncts.
From a prevention standpoint, epidemiologic data consistently show that regular physical activity reduces the incidence of several common malignancies—particularly breast, colorectal, lung, bladder, and gastric cancers—by approximately 10–20%. These protective effects are explained mechanistically by exercise-induced reductions in chronic inflammation, improved metabolic regulation, enhanced immune surveillance, and greater genomic stability. For physicians, this reinforces exercise counseling as a primary prevention strategy, not simply a wellness recommendation.
In patients with established cancer, the review highlights compelling survival benefits. Observational and cohort studies indicate that regular exercise is associated with 40–50% reductions in cancer-specific mortality, especially in breast, colorectal, and prostate cancers. Clinically, these survival advantages parallel or exceed the benefit of some systemic therapies, underscoring why exercise should be integrated into standard oncology pathways rather than offered as an optional add-on.
At the molecular level, exercise favorably remodels the tumor microenvironment. Contracting skeletal muscle releases myokines—most notably interleukin-6 (IL-6)—that exert anti-inflammatory and immune-activating effects when released during exercise. This contrasts sharply with the pro-tumorigenic role of chronically elevated IL-6 seen in cancer and obesity. Exercise-induced IL-6 mobilizes natural killer (NK) cells and CD8⁺ T cells, improves immune cell infiltration into tumors, and limits immune evasion. For clinicians using immunotherapies, this has direct relevance: exercise may help convert immunologically “cold” tumors into “hot” ones, thereby enhancing responsiveness to immune checkpoint inhibitors.
Exercise also exerts powerful effects on metabolic and oncogenic signaling pathways. Regular physical activity improves insulin sensitivity and lowers circulating insulin and insulin-like growth factor-1 (IGF-1), both of which drive tumor proliferation through PI3K/Akt/mTOR signaling. By activating AMP-activated protein kinase (AMPK) and suppressing mTOR, exercise directly inhibits pathways central to cancer cell growth and survival. These findings provide a mechanistic rationale for combining exercise with targeted therapies that act on similar signaling axes.
Hormonal modulation represents another clinically important mechanism. In premenopausal women, exercise can reduce lifetime exposure to estrogen and progesterone through delayed menarche or altered menstrual cycling, lowering risk for hormone-sensitive cancers. In postmenopausal women, exercise reduces adipose tissue–derived estrogen production and shifts estrogen metabolism toward less biologically active metabolites. For physicians managing breast and endometrial cancer risk, these effects reinforce exercise as a nonpharmacologic endocrine intervention.
Beyond disease control, the review emphasizes exercise’s role in treatment tolerance and quality of life. Exercise consistently reduces cancer-related fatigue, preserves muscle mass and bone density, improves cardiovascular fitness, and mitigates chemotherapy- and radiation-related toxicities. Importantly, higher-intensity aerobic and resistance programs often outperform low-intensity activity, challenging the misconception that cancer patients should only engage in gentle movement.
The authors also highlight emerging evidence that exercise enhances drug delivery by normalizing tumor vasculature, reducing hypoxia, and improving intratumoral perfusion—mechanisms that may increase the effectiveness of chemotherapy, radiotherapy, and immunotherapy alike. For oncologists, this raises the possibility that exercise could function as a biologic sensitizer, improving therapeutic efficacy without adding toxicity.
Despite these strengths, the review acknowledges key gaps: optimal exercise “dose,” timing relative to treatment, and cancer-specific prescriptions remain incompletely defined. Adherence barriers, patient heterogeneity, and limited large-scale randomized trials constrain translation into formal guidelines.
In conclusion, this review provides strong mechanistic and clinical justification for embedding structured exercise into cancer prevention, treatment, and survivorship care. For patients, exercise emerges as a powerful, accessible tool to improve outcomes and quality of life. For physicians, it represents an evidence-based intervention that should be prescribed with the same intentionality as other components of comprehensive oncology care Reference: European Journal of Cancer Prevention DOI: 10.1097/CEJ.0000000000000989
