Management of muscle wasting in cancer-associated cachexia: understanding gained from experimental studies

Background: Cancer-associated cachexia is a syndrome of progressive wasting of body energy (adipose) and protein (skeletal muscle) reserves. Cachexia occurs in a majority of advanced cancer patients. Extensive loss of muscle mass is one factor likely to be associated with fatigue in cancer patients.

Methods: Research with animal models of cancer-associated cachexia that have focused on the processes of muscle protein synthesis and degradation are reviewed in this article. Modulation of the production or action of anabolic and catabolic factors known to regulate muscle protein synthesis and degradation have been employed to identify causal factors in muscle wasting.

Results: Impaired muscle protein synthesis and activation of catabolism participate in cancer-associated muscle atrophy. The relative roles of multiple factors, including a low level of physical activity, poor nutritional status, and secretion of catabolic mediators of host or tumor origin, are discussed herein. A diversity of putative mediators has been identified, and a number of common themes are beginning to emerge.

Conclusions: Multiple distinct catabolic profiles exist in animal models of cancer-associated muscle wasting. The presence of these catabolic phenotypes in cancer patients must be determined, and the application of successful treatments will depend on our ability to determine which categories of patients experience the greatest benefit.