Myokines in cancer: bridging molecular mechanisms to biomarker discovery and therapeutic innovation

Exercise can regulate the physiological functions of the body by inducing the secretion of myokines, which are bioactive factors mainly secreted by muscle cells. This review classifies myokines based on their functional characteristics, including metabolic regulation (such as myostatin, interleukin-6), neuroregulation (brain-derived neurotrophic factor), cell proliferation/differentiation regulation (myogenic proteins), immune regulation (tumor necrosis factor- alpha), and factors involved in angiogenesis and extracellular matrix remodeling (such as connective tissue growth factor).Cancer, as a consuming disease, often accompanies muscle atrophy and depletion in its advanced stage, thereby affecting the normal secretion of myokines. Increasing research evidence indicates that myokines play a dual regulatory role in the occurrence and development of cancer. Some myokines (such as interleukin-6, tumor necrosis factor- alpha) have environment-dependent functions and can exhibit pro-cancer or anti-cancer effects depending on the microenvironment; while factors such as myostatin show stable anti-tumor potential by regulating key molecular pathways such as the PI3K/AKT pathway, epithelial-mesenchymal transition, and HIF-1α. It is worth noting that muscle cell factors can indirectly influence the disease outcome of cancer by regulating key cells and structures in the tumor microenvironment (such as tumor-associated macrophages, regulatory T cells, and cancer-associated fibroblasts), as well as by participating in the angiogenesis process. At the clinical application level, muscle cell factors are expected to become potential biomarkers for cancer diagnosis and prognosis assessment (such as elevated irisin levels in patients with renal cancer and elevated interleukin-6 levels in patients with bile duct cancer). They also have great potential as therapeutic targets. For example, MSTN inhibitors can effectively alleviate cancer cachexia symptoms, and the combination of anti-interleukin-6 treatment with immune checkpoint blockade therapy can produce a significant synergistic therapeutic effect. This review systematically summarizes the latest research progress on the molecular interaction mechanisms mediated by myokines in cancer, emphasizing their potential for translational applications in precision oncology. Myokines not only regulate the physiological functions of the musculoskeletal system, but also have a close association with the occurrence and development of cancer. The intrinsic connection between myokines and muscle atrophy as well as cancer-related cachexia still requires further in-depth exploration. As emerging biomarkers, myokines can be combined with various diagnostic and therapeutic techniques, which is expected to further improve the survival rate of cancer patients, protect muscle function, and also provide new research ideas for exploring the interrelationship between muscles and cancer and the pathogenesis of related muscle diseases.