Mechanism-Based Therapeutic Approaches to Cachexia

Abstract

Cachexia is a multifactorial syndrome characterized by body weight loss, depletion of adipose tissue and skeletal muscle mass, and marked alterations of the metabolic homeostasis.The occurrence of cachexia significantly impinges on patient's 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 are long known contributing factors, the mechanisms leading to inflammation and metabolic alterations were clarified later on. On these premises, several therapeutic approaches were proposed. Most of them are in the pre-clinical phase, but some already reached the clinical experimentation. The present review will focus on treatment options proposed on the basis of mechanistic alterations. In this regard, in addition to nutritional and anti-inflammatory strategies, also approaches based on perturbation of specific signal transduction pathways are taken into consideration.

Role of interleukin-6 in cachexia

“…This suggests that in models of IL-6 induced cachexia; NF- κB activation is additive but not essential to regulate muscle wasting. There may also be a role for indirect IL-6 signaling through muscle AMPK activation, which can suppress muscle mTOR/S6 signaling related to protein synthesis [24, 27]. Interestingly, exercise may be beneficial for countering the effects of IL-6 on muscle wasting[48].…”

Maintaining ordinariness around food: partners’ experiences of everyday life with a dying person

“…In the challenge of doing their best, the participants in this study were focused on their partners' food intake during the whole illness trajectory. It is reasonable to assume that their distress could have been somewhat relieved if they had known more about the natural dying process and metabolic changes related to severe cachexia (Stephens & Fearon 2007, Penna et al 2013) and if they had been given support from healthcare professionals in handling their feelings of inadequacy as partners. Even though the participants did not explicitly talk about guilt, these findings relate to previous studies of guilt and shame among family care givers in palliative home care (Harst€ ade 2012).…”

“…Among people with advanced-stage cancer or other severe chronic diseases, weight loss and loss of appetite are common symptoms that are often referred to as being part of cachexia, a stage of unintentional weight loss due to decreased food intake and metabolic induction of muscle breakdown that cannot be nutritionally reversed (Penna et al 2013). Other troubles related to the disease and/or treatment, such as fatigue, nausea (Matzo & Witt Sherman 2010), bowel obstruction (Fuhrman & Herrmann 2006, Clark et al 2012 and changes in smell (Bernhardson et al 2008) and taste (Schiffman 2007, Bernhardson et al 2008), add to the decline in appetite and hamper the ability to eat (Stepp & Pakiz 2001, Tan & Fearon 2008.…”

Cancer inflammation and inflammatory biomarkers: can neutrophil, lymphocyte, and platelet counts represent the complexity of the immune system?

“…For example, chronic inflammation due to infectious diseases is believed to be responsible for more than 15% of known cancers to date [4], while inflammatory mediators are known to directly promote malignant transformation in experimental models [5]. On the other hand, once cancer progresses, it leads to a chronic inflammatory-like state which, through altered aminoacid metabolism among other mechanisms [6] causes cachexia, the main cause of death in patients with cancer.…”