Novel molecular targets of muscle wasting in cancer patients.

Abstract

Cancer-associated muscle wasting affects many patients and leads to reduced patient function, decreased quality of life and poor responses to surgical and oncological treatments. Despite advancements in the understanding of its pathophysiology, no current treatment or accepted strategy for successful management exists. In this review, we provide an update on potential novel therapeutic targets in cancer cachexia. Recent research has focused on molecular mechanisms underlying cancer-associated muscle wasting, allowing identification of potential therapeutic targets and the development of several promising drugs. However, due to the multifactorial and patient-specific pathogenesis of cachexia, the demonstration of a measurable and meaningful clinical effect in randomized controlled trials has proven difficult. Potential novel targets such as circulating macrophage inhibitory cytokine 1/growth differentiation factor 15 and ZRT/IRT-like protein 14 have shown relevance in animal models, but their therapeutic manipulation has yet to be translated to patients. Increasing evidence has suggested that a single therapy may not be successful and a targeted, multimodal approach is required. The management of cancer-associated muscle wasting is complex. Future clinical trials should focus on early multimodal therapeutic interventions involving targeted therapies, with careful deliberation of chosen nutritional and functional outcomes.