Pathogenesis of muscle wasting in cancer cachexia: targeted anabolic and anticatabolic therapies

Abstract

Cancer-related muscle loss, or cachexia, is the cause of death for approximately 2 million people worldwide and severely reduces quality of life. The degree of cachexia is inversely correlated with survival time; however, the exact mechanisms behind cancer-induced muscle wasting remain under investigation. Cytokines such as tumor necrosis factor-alpha trigger degradatory pathways through nuclear factor-kappaB signaling that activate the ubiquitin-proteasome system and muscle proteolysis. Androgen treatment has been shown to reduce inflammatory cytokines and even stimulate anti-inflammatory cytokine production. Amino acid supplementation has been shown to induce muscle protein synthesis in ovarian cancer patients. Targeted anabolic therapies aimed at preventing or reversing cancer cachexia might involve the combined use of androgens and amino acids working concurrently to enhance muscle protein synthesis and reduce muscle protein breakdown. Additional focused clinical studies are needed to identify muscle-specific targets or biomarkers for defined therapeutic approaches to slow or prevent cancer cachexia. In this review, we summarize the pathogenesis of cancer-related muscle wasting and discuss potential interventions at reversing or preventing cancer-related muscle loss.