Exercise-induced myokines and the muscle-tumor axis in obesity-driven gynecological cancers: a narrative review.

Obesity represents a cornerstone risk factor for gynecological malignancies, particularly endometrial carcinoma and specific ovarian cancer subtypes. This association is driven by a systemic milieu of chronic low-grade inflammation, adipokine dysregulation, and hyperinsulinemia. Conversely, skeletal muscle is now recognized as a dynamic endocrine organ that, through contraction-induced secretion of myokines, orchestrates a "muscle-tumor axis" capable of antagonizing pro-tumorigenic signaling. This narrative review aims to synthesize current evidence regarding the role of exercise-induced myokines in obesity-driven gynecological cancers, elucidating the mechanisms through which these molecules reshape the systemic and tumor microenvironment. A comprehensive search of PubMed/MEDLINE, Scopus, and Web of Science was conducted up to early 2026, focusing on myokine signaling, exercise physiology, and gynecological oncology. Chronic obesity significantly impairs the skeletal muscle secretory profile, fostering an environment conducive to tumor progression. Exercise-induced secretion of key myokines, specifically IL-15, Irisin (FNDC5), SPARC, and FGF21, counteracts these effects through multiple mechanisms. Irisin and SPARC directly inhibit cell proliferation and epithelial-mesenchymal transition (EMT) by modulating the PI3K/Akt/mTOR pathway. IL-15 enhances anti-tumor immune surveillance by promoting the recruitment and cytotoxic activity of Natural Killer (NK) cells. Furthermore, FGF21 and Irisin facilitate metabolic reprogramming by inducing adipose tissue browning and restoring the insulin/IGF-1 axis homeostasis. Myokines may serve as critical biological mediators linking physical activity to cancer protection. Understanding these exercise-induced molecular transducers may provide a robust rationale for developing "precision exercise" protocols as a tailored non-pharmacological strategy to improve oncological outcomes in gynecological cancer patients.