Extracellular vesicles in cancer-associated cachexia: molecular mechanisms and therapeutic perspectives

Abstract

Cancer-associated cachexia (CAC) is increasingly recognized as a systemic metabolic disorder characterized by progressive skeletal muscle wasting, adipose tissue remodeling, chronic inflammation, and profound metabolic dysfunction, which collectively compromise therapeutic efficacy and patient survival. Although accumulating experimental studies have demonstrated that tumor-derived extracellular vesicles (EVs) contribute to CAC, current evidence is largely fragmented, with most studies focusing on individual EV cargoes or isolated signaling pathways rather than providing an integrated mechanistic perspective. This review evaluates representative experimental studies describing how tumor-derived EVs regulate skeletal muscle atrophy, adipose tissue remodeling, inflammatory responses, and metabolic reprogramming during cachexia progression. We further summarize recent advances in EV-based biomarkers and therapeutic strategies, while discussing current challenges and future directions for clinical translation. In particular, circulating EV-associated molecules, including glucose-regulated protein 75 (GRP75) and specific miRNAs, have shown promise as diagnostic and prognostic biomarkers. Unlike previous reviews that primarily focus on individual EV cargoes or signaling pathways, this review integrates representative experimental evidence spanning molecular mechanisms, biomarker discovery, and therapeutic intervention, thereby providing a comprehensive overview of the multifaceted roles of tumor-derived EVs in CAC and their translational potential as biomarkers and therapeutic targets.