Cancer Cachexia: Molecular Targets and Pathways for Diagnosis and Drug Intervention

Angie      M.Y. Shum; Patsie      Polly

Abstract

Cancer cachexia is a highly debilitating paraneoplastic disease observed in more than 50% of patients with advanced cancers and directly contributes to 20% of cancer deaths. Skeletal muscle wasting is a prominent feature of the disease and is believed to result from the loss of balance between protein synthesis and degradation. Quality of life and prognosis are severely compromised in patients with cancer cachexia. Despite current knowledge on the mediators involved in cancer cachexia, treatment targeting a single molecule has rendered limited effectiveness. This article aims to review the mediators of cancer cachexia and interventions attempted in the literature and discuss the common pathways leading to protein loss that these mediators modulate during cachexia. We believe that by targeting downstream effectors that are common in these pathways, a better therapeutic approach to reverse muscle wasting and maintain muscle function during cancer cachexia will be achieved.

Keywords: Cancer cachexia, mediators, metabolism, muscle wasting, signalling, transcription factors, RORα, Calcineurin, RNA-dependent, Protein, myotubes.