Exercise oncology emerges as discovery engine for cancer therapies

A patient with advanced cancer sits in an oncology clinic, too weak from treatment and disease to walk on a treadmill or join a supervised exercise program. Yet researchers now believe that patient might still access the very benefits that exercise provides—not through movement, but through drugs designed to mimic what happens inside the body when someone exercises.

This shift in thinking comes from a new framework proposed by Dr. Emma S. Kurz at Massachusetts General Hospital and Memorial Sloan Kettering Cancer Center, alongside Prof. Dafna Bar-Sagi at NYU Langone Hospital. In a perspective published in EXO – Beyond the Cell, they argue that exercise oncology—the study of how physical activity affects cancer outcomes—should be reimagined as a discovery platform rather than simply a prescription tool. The insight is straightforward but consequential: if researchers can identify the specific molecular mechanisms that exercise activates in the body, they might be able to bottle those mechanisms as medicines for patients too ill to exercise.

The problem they're addressing is real. While regular exercise is well-established to improve outcomes for many cancer patients, those with advanced disease often cannot participate. Cachexia—the wasting that accompanies late-stage cancer—frailty from chemotherapy, and treatment-related toxicities leave these patients unable to engage in physical activity. They are locked out of a therapeutic benefit that might help them, simply because their bodies cannot tolerate the intervention.

The authors point to three emerging areas where this reframing is already bearing fruit. The first involves metabolic changes triggered by exercise. When people exercise, their bodies produce lactate, a metabolite long dismissed as mere metabolic waste. Recent studies show that circulating lactate can reprogram CD8⁺ T cells—immune cells crucial for fighting cancer—toward a more aggressive anti-tumor state. Remarkably, administering lactate alone, without exercise, can reproduce some of these immune effects. This suggests that exercise-induced circulating factors, which researchers call "exerkines," could become drug candidates in their own right.

The second pathway involves the gut microbiome. Exercise reshapes the microbial communities living in the digestive tract, altering their metabolism and increasing production of compounds like formate. Preclinical evidence indicates these microbiome changes enhance anti-tumor immunity and improve how patients respond to checkpoint inhibitor drugs—a major class of cancer immunotherapy. This opens the door to microbiome-based interventions: fecal transplants, targeted bacterial therapies, or metabolite supplements that might capture exercise's benefits without requiring a patient to move.

The third example focuses on IL-15, a cytokine released during exercise that influences immune surveillance. In pancreatic cancer models, activating the IL-15 pathway alone—without any exercise—can trigger important anti-tumor immune responses. Again, the principle holds: the mechanism can be separated from the activity.

Kurz and Bar-Sagi are careful to emphasize that this framework is not meant to replace exercise in cancer care. Physical activity produces complex, whole-body effects that no single drug is likely to fully replicate. Rather, they propose that discoveries from exercise biology should complement clinical exercise programs, expanding the toolkit for patients who cannot exercise while also informing the next generation of precision cancer therapies. The reframing transforms exercise oncology from a field that validates a lifestyle intervention into a field that mines physiology for therapeutic targets—turning the treadmill into a laboratory, and the laboratory into a pharmacy for patients who need it most.