Skeletal muscle atrophy and dysfunction contribute to morbidity and mortality in patients with cancer. Cachexia pathophysiology is highly complex, given that perturbations to the systemic cancer environment and the interaction with diverse tissues can contribute to wasting processes. Systemic interleukin 6 (IL-6) and glycoprotein 130 (gp130) receptors signaling have established roles in some types of cancer-induced muscle wasting through disruptions to protein turnover and oxidative capacity. Although exercise has documented benefits for cancer prevention and patient survival, there are significant gaps in our understanding of muscle adaptation and plasticity during severe cachexia. Preclinical models have provided valuable insight into the adaptive potential of muscle contraction within the cancer environment. We summarize the current understanding of how resistance-type exercise impacts mechanisms involved in cancer-induced muscle atrophy and dysfunction. Specifically, the role of IL-6 and gp130 receptors in the pathophysiology of muscle wasting and the adaptive response to exercise is explained. The discussion includes current knowledge gaps and future research directions needed to improve preclinical research and accelerate clinical translation in human patients with cancer.
Keywords: cancer cachexia; eccentric contractions; oxidative metabolism; protein breakdown; protein synthesis.