Cancer cachexia: A tumor-driven disorder of whole-body homeostasis

Cancer cachexia is a systemic metabolic syndrome driven by tumor-induced disruption of whole-body homeostasis. Characterized by skeletal muscle atrophy and adipose tissue loss, cachexia leads to functional decline, impaired quality of life, reduced treatment tolerance, and poor survival across multiple malignancies. Emerging evidence indicates that cachexia arises from complex and dynamic interactions between tumors and host organ systems, including immune, metabolic, endocrine, and neural networks, that collectively reshape energy balance, immune function, and tissue integrity. Despite its profound clinical impact, effective therapies remain limited, reflecting incomplete mechanistic understanding and the absence of integrated clinical frameworks. Here, we review recent advances in cachexia biology, including tumor-host signaling, multiorgan metabolic remodeling, and neuroendocrine regulation. We further propose a tumor-centric framework in which cachexia represents a progressive collapse of systemic homeostasis and outline translational strategies to guide mechanism-informed therapeutic interventions. Cancer cachexia is a tumor-driven collapse of systemic homeostasis rather than a passive consequence of advanced disease. In this review, Zhang et al. define a tumor-centric framework in which tumor-derived signals rewire immune, metabolic, and neuroendocrine networks across organs, establishing self-sustaining catabolic feedback loops. This model provides a conceptual foundation for biomarker-guided and mechanism-based therapeutic strategies.