Neural Mechanisms of Cancer Cachexia

Simple Summary Cancer cachexia is a devastating wasting syndrome that occurs in many illnesses, with signs and symptoms including anorexia, weight loss, cognitive impairment and fatigue. The brain is capable of exerting overarching homeostatic control of whole-body metabolism and is increasingly being recognized as an important mediator of cancer cachexia. Given the increased recognition and discovery of neural mechanisms of cancer cachexia, we sought to provide an in-depth review and update of mechanisms by which the brain initiates and propagates cancer cachexia programs. Furthermore, recent work has identified new molecular mediators of cachexia that exert their effects through their direct interaction with the brain. Therefore, this review will summarize neural mechanisms of cachexia and discuss recently identified neural mediators of cancer cachexia. Nearly half of cancer patients suffer from cachexia, a metabolic syndrome characterized by progressive atrophy of fat and lean body mass. This state of excess catabolism decreases quality of life, ability to tolerate treatment and eventual survival, yet no effective therapies exist. Although the central nervous system (CNS) orchestrates several manifestations of cachexia, the precise mechanisms of neural dysfunction during cachexia are still being unveiled. Herein, we summarize the cellular and molecular mechanisms of CNS dysfunction during cancer cachexia with a focus on inflammatory, autonomic and neuroendocrine processes and end with a discussion of recently identified CNS mediators of cachexia, including GDF15, LCN2 and INSL3.