title: Mechanisms of anorexia-cachexia syndrome and rational for treatment with selective ghrelin receptor agonist.
abstract: Cancer cachexia is a multi-organ, multifactorial and often irreversible syndrome affecting many patients with cancer. Cancer cachexia is invariably associated with weight loss, mainly from loss of skeletal muscle and body fat, conditioning a reduced quality of life due to asthenia, anorexia, anaemia and fatigue. Treatment options for treating cancer cachexia are limited. The approach is multimodal and may include: treatment of secondary gastrointestinal symptoms, nutritional treatments, drug, and non-drug treatments. Nutritional counselling and physical training may be beneficial in delaying or preventing the development of anorexia-cachexia. However, these interventions are limited in their effect, and no definitive pharmacological treatment is available to address the relevant components of the syndrome. Anamorelin is a first-in-class, orally active ghrelin receptor agonist that binds and stimulates the growth hormone secretagogue receptor centrally, thereby mimicking the appetite-enhancing and anabolic effects of ghrelin. It represents a new class of drug and an additional treatment option for this patient group, whose therapeutic options are currently limited. In this review we examine the mechanisms of anamorelin by which it contrasts catabolic states, its role in regulation of metabolism and energy homeostasis, the data of recent trials in the setting of cancer cachexia and its safety profile.
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Criscitiello
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gelao
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy; Department of Health Science, Università di Milano, Milano, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pravettoni
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Locatelli
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Minchella
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Leo
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Liuzzi
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Milani
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Massaro
authors.affiliation: Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine, Via Ripamonti 435, 20133 Milano, Italy. Electronic address: giuseppe.curigliano@ieo.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
mesh_terms: D000818:Animals; D000855:Anorexia / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D054440:Receptors, Ghrelin / Q000819:agonists* / Q000378:metabolism; D013577:Syndrome
chemical_list: D006834:Hydrazines; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C000593861:anamorelin
keywords: Anamorelin; Cancer cachexia; Ghrelin receptor