Cancer cachexia: an unmet need in cancer treatment

Abstract

Cachexia is one of the most distressing and devastating experiences for cancer patients. It is now considered a complex, multifacto‐ rial metabolic syndrome characterized by anorexia, progressive and uncontrollable weight loss, fatigue, progressive depletion of adipose tissue and skeletal muscle, sys‐ temic inflammation, insulin resistance, abnormalities in the metabolism of car‐ bohydrate, protein and lipid, as well as impaired immune function [1–3]. Within recent years substantial progress has been made in unraveling the underlying mech‐ anisms of cancer cachexia [3–6]. Numer‐ ous cytokines including TNF‐α, IL‐1, IL‐6 and IFN‐γ have been postulated to play an important role in cachexia devel‐ opment [3–6]. These cytokines have been directly or indirectly implicated in can‐ cer‐induced muscle wasting by activating the ATP–ubiquitin–proteasome‐depen‐ dent proteolytic pathway and profound anorexia by mimicking leptin signaling and suppressing orexigenic ghrelin and neuropeptide Y signaling [3–6]. Cachexia significantly impairs quality of life and response to antitumor treatments in cancer patients. Therefore, it strongly influences morbidity and mortality. In addition, cachexia is perceived as a harbin‐ ger of death, and therefore it has profound psychological and emotional impact on both patients and their families [7]. In 2011, international expert panel members agreed on the following defini‐ tion for cancer cachexia: “Cancer cachexia is a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is char‐ acterized by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metab‐ olism” [3]. The panel has also defined the criteria for diagnosing cachexia in cancer patients: