Development and progression of cancer cachexia: Perspectives from bench to bedside

Cancer cachexia (CC) is a devastating syndrome characterized by weight loss, reduced fat mass and muscle mass that affects approximately 80% of cancer patients and is responsible for 22%-30% of cancer-associated deaths. Understanding underlying mechanisms for the development of CC are crucial to advance therapies to treat CC and improve cancer outcomes. CC is a multi-organ syndrome that results in extensive skeletal muscle and adipose tissue wasting; however, CC can impair other organs such as the liver, heart, brain, and bone as well. A considerable amount of CC research focuses on changes that occur within the muscle, but cancer-related impairments in other organ systems are understudied. Furthermore, metabolic changes in organ systems other than muscle may contribute to CC. Therefore, the purpose of this review is to address degenerative mechanisms which occur during CC from a whole-body perspective. Outlining the information known about metabolic changes that occur in response to cancer is necessary to develop and enhance therapies to treat CC. As much of the current evidences in CC are from pre-clinical models we should note the majority of the data reviewed here are from preclinical models.