From bench to bedside: updates in basic science, translational and clinical research on muscle fatigue in cancer cachexia.

Abstract

Cancer cachexia is a syndrome of loss of weight and muscle mass that leads to reduced strength, poor physical performance and functional impairment. Muscular fatigue is a distressing syndrome that patients with cachexia suffer from and can impair quality of life. Here, we review recent updates in muscular fatigue in cancer cachexia research with a focus on mechanisms, biomarkers and potential therapies. Both in mice and humans, research has shown that muscle fatigue can be independent of muscular atrophy and can happen early in cancer development or in precachexia. Inflammatory pathways, mitochondrial dysfunction and gut microbiota have recently been studied to play an important role in muscle fatigue in preclinical models. Exercise can target these pathways and has been studied as a therapeutic intervention to improve muscle fatigue. Heightened inflammation within muscle, altered muscle function and muscle fatigue can begin prior to clinical evidence of cachexia, making early recognition and intervention challenging. The emergence of cachexia mouse models and translational and clinical research studying muscle fatigue will hopefully lead to new therapies targeting the underlying mechanisms of cancer cachexia. Exercise will need to be tested in larger randomized studies before entering into daily practice.