The nervous system as a systemic organizer of cancer-associated cachexia.

Abstract

Cancer-associated cachexia (CAC) is a progressive, multiorgan wasting syndrome that critically limits treatment response and survival. In CAC, the nervous system senses, amplifies, and coordinates responses to a broad range of tumor-induced perturbations, including both direct tumor-derived factors and the resulting systemic disturbances in inflammation, metabolism, and immunity. By dysregulating central neural circuits and remodeling peripheral innervation, tumor-hijacked neural coordination drives both anorexia and multiorgan wasting, forming a self-reinforcing cachexia loop. Additionally, treatment-associated neurotoxicity further augments dysfunction across the central and peripheral nervous systems. In this review, we synthesize evidence from patient studies and animal models to examine how tumors co-opt the nervous system to systemically organize cachexia, thereby providing a pathophysiological framework for studying early disease detection, biomarker development, and mechanism-based intervention for CAC.