Cancer-Associated Cachexia: Bridging Clinical Findings with Mechanistic Insights in Human Studies

Abstract Cancer-associated cachexia (CAC) is a chronic wasting disease typically associated with advanced cancer, resulting in progressive and debilitating loss of function and poor tolerance to anticancer therapy. Preclinical animal models have identified various potential mechanisms and mediators, which have had limited translational success in clinical trials. This review focuses on human studies and discusses the clinical phenotyping of CAC using imaging-derived body composition, quality-of-life and functional measures, existing evidence for mediators, current therapeutic options, and future directions to advance the field. Identifying mechanisms driving CAC and targeting them are expected to improve the quality of life, treatment efficacy, and survival. Significance: CAC represents a significant clinical unmet need. Despite its high prevalence and associated mortality and morbidity, there are currently no globally approved effective therapies. This review provides a comprehensive overview of human studies aimed at defining CAC clinically and identifying mediators underlying it that are revealing effective health interventions. Furthermore, we highlight ongoing international efforts to advance our understanding of CAC.