Exercise has long been celebrated as a remedy for body and mind, a ritual that strengthens the heart, lifts the mood, and staves off disease. Yet beneath the sweat and the rhythm of a pounding treadmill lies a hidden story at the molecular level. Scientists have been chasing the question of exactly how physical activity can slow cancer, a puzzle that has remained elusive—until now. A new study published in the Proceedings of the National Academy of Sciences reveals that the answer might lie in how exercise rewires our muscles to seize the nutrients that tumors would otherwise consume.
A Race Against Tumors
To uncover this secret, researchers turned to a familiar laboratory ally: the mouse. Mice were injected with breast cancer cells and divided into groups, some fed a high-fat diet and some a normal diet. In the high-fat group, wheels were placed in cages, allowing mice to run voluntarily. But this wasn’t just a casual observation of furry athletes. Scientists used sophisticated tracer studies with labeled glucose and glutamine to track exactly where energy was going in the body.
After just four weeks, the results were startling. Mice that had chosen to exercise had significantly smaller tumors compared to those that had remained sedentary, even when both groups were on the same diet. The study authors describe it vividly: “Obese mice which underwent 4 weeks of voluntary wheel running after tumor injection exhibited nearly a 60% reduction in tumor size. The exercised mice had greater lean mass and lower fat mass than their nonexercised, obese counterparts, with plasma glucose and insulin concentrations comparable to the sedentary chow fed controls.”
It wasn’t only the breast cancer models that showed promise. Mice with a type of melanoma, typically unaffected by obesity, also experienced reduced tumor sizes after four weeks of exercise. Glucose uptake by tumors decreased, confirming that exercise redirected this essential fuel toward muscles instead of malignant cells. Even mice that engaged in “prehabilitation”—exercise before tumors were introduced—enjoyed similar benefits, suggesting that early conditioning primes the body for resilience. “These observations may be due to an earlier achievement and maintenance of body composition or overall fitness (VO2 peak) with early exercise exposure,” the authors explain.
Muscles as Nutrient Gatekeepers
The study paints a picture of muscles as energetic guardians, actively diverting glucose and oxygen from tumors. During exercise, both skeletal and cardiac muscles ramp up their uptake of 2-deoxyglucose, leaving tumors starving for the same fuel. It is as if the body is quietly reclaiming resources for the benefit of healthy tissues, subtly reshaping metabolism to slow the enemy within.
Yet glucose repartitioning is only one part of a more complex story. The researchers also identified 417 genes related to energy metabolism that were expressed differently in exercised mice. Among these changes, a downregulation of mTOR—a protein known to support tumor growth—may contribute to slowing cancer progression. Tumors, it seems, not only lose access to energy but also to the molecular signals that promote their expansion.
Clues in Human Muscle
While these findings are rooted in mice, the implications for humans are compelling. The research team examined gene expression in women with breast cancer and conducted a meta-analysis of skeletal muscle responses to exercise. They found similar patterns: exercise upregulated genes involved in glutamine and leucine channeling in human muscle tissue. Although differences in gene expression did not vary noticeably with exercise intensity—likely due to small sample sizes—the molecular echoes suggest a conserved mechanism across species.
Researchers are cautious but hopeful. Metabolic pathways are remarkably similar across mammals, hinting that humans may benefit from the same protective shift of nutrients away from tumors. Integrating fitness into cancer care could enhance treatment, support patient resilience, and even inspire new therapeutic approaches.
Rethinking Fitness and Cancer
The study’s authors envision a future where exercise is more than a preventative measure—it becomes an active component of therapy. “We anticipate that this work may lay the groundwork to reveal key insights into the role of systemic adaptations to exercise in broader antitumor therapies. Further, examination of the role of fitness on the molecular pathways altered by exercise may uncover new therapeutic targets in precision oncology, particularly in patients who cannot tolerate exercise,” they explain.
This research reframes exercise from a simple health habit to a form of metabolic strategy. Each stride, each pedal, each heartbeat in motion is a signal to the body to protect itself, to nourish muscles instead of tumors, and to fortify resilience. It invites a more intimate understanding of movement, not just as motion, but as medicine at the cellular level.
Why This Matters
Understanding how exercise alters metabolism in cancer opens doors to a new era of patient care. Prehabilitation programs could prime patients before treatment, while targeted exercise regimens might amplify the effectiveness of existing therapies. Even for patients unable to perform vigorous activity, insights from these studies could guide pharmaceutical or molecular interventions that mimic exercise’s benefits.
In the end, the research illuminates a profound truth: the body is not passive in the face of disease. Movement can orchestrate a quiet rebellion against tumors, redirecting energy, recalibrating metabolism, and activating molecular pathways that slow cancer’s progress. This is the story of muscles as guardians, exercise as a weapon, and science uncovering the extraordinary intelligence of life itself.
More information: Brooks P. Leitner et al, Precancer exercise capacity and metabolism during tumor development coordinate the skeletal muscle–tumor metabolic competition, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2508707122
