LAUSR

Simple Summary An uncontrollable loss in the skeletal muscle of cancer patients which leads to a significant reduction in body weight is clinically referred to as cancer cachexia (CC). While factors derived from the tumor environment which trigger various signaling pathways have been identified, not much progress has been made clinically to effectively prevent muscle loss. Deeper insights into the transcriptional and epigenetic regulation of muscle catabolic genes may shed light on key regulators which can be targeted to develop new therapeutic avenues. Abstract Cancer cachexia (CC) is a multifactorial syndrome characterized by a significant reduction in body weight that is predominantly caused by the loss of skeletal muscle and adipose tissue. Although the ill effects of cachexia are well known, the condition has been largely overlooked, in part due to its complex etiology, heterogeneity in mediators, and the involvement of diverse signaling pathways. For a long time, inflammatory factors have been the focus when developing therapeutics for the treatment of CC. Despite promising pre-clinical results, they have not yet advanced to the clinic. Developing new therapies requires a comprehensive understanding of how deregulated signaling leads to catabolic gene expression that underlies muscle wasting. Here, we review CC-associated signaling pathways and the transcriptional cascade triggered by inflammatory cytokines. Further, we highlight epigenetic factors involved in the transcription of catabolic genes in muscle wasting. We conclude with reflections on the directions that might pave the way for new therapeutic approaches to treat CC.