Mechanisms to explain wasting of muscle and fat in cancer cachexia

Abstract

Purpose of review: To describe the most relevant recent findings concerning the molecular mechanisms involved in both fat and muscle tissues in cachectic cancer patients.

Recent findings: Relevant progress has been made in the mechanism of signalling protein metabolism in skeletal muscle. PI3K has a dual role inhibiting protein degradation by inhibition of Atrogin-1 and MuRF1 gene expression and facilitating AKT phosphorylation, leading to increased protein synthesis. Interestingly, Caspase-3 activity is intimately associated with myofibrillar protein degradation in muscle tissue. With respect to fat metabolism, increased lipolysis in human cancer cachexia seems to be directly connected to increased hormone-sensitive lipase activity.

Summary: The results and findings described in this review represent important progress in wasting disease mechanisms and may provide hints for future therapeutic approaches in cancer cachexia.