Mechanism-based therapeutic approaches to cachexia

Cachexia is a multifactorial syndrome characterized by body weight loss, depletion of adipose tissue and skeletal muscle mass, and marked alterations in the metabolic homeostasis. The occurrence of cachexia significantly impinges on patients' morbidity and mortality, and on quality of life. Inflammation, anorexia/malnutrition, alterations of protein and lipid metabolism are among the main mechanisms involved in the development of cachexia. While anorexia and malnutrition have long been known to be contributing factors, the mechanisms leading to inflammation and metabolic alterations were clarified much later. On these premises, several therapeutic approaches were proposed. Most of them are in the preclinical phase, but some have already reached the clinical experimentation stage. This review focuses on treatment options proposed on the basis of mechanistic alterations. In this regard, in addition to nutritional and anti-inflammatory strategies, approaches based on perturbation of specific signal transduction pathways are taken into consideration.