Deliberation on debilitating condition of cancer cachexia: Skeletal muscle wasting

BackgroundCancer cachexia is a debilitating syndrome associated with marked body loss because of muscular atrophy and fat loss. There are several mechanisms contributing to the pathogenesis of cachexia. The presence of the tumor releases cytokines from inflammatory and immune cells, which play a significant role in activating and deactivating certain pathways associated with protein, carbohydrate, and lipid metabolism. This review focuses on various cascades involving an imbalance between protein synthesis and degradation in the skeletal muscles. ObjectivesThis study aimed to elucidate the mechanisms involved in skeletal muscle wasting phenomenon over the last few years. MethodsThis article briefly overviews different pathways responsible for muscle atrophy in cancer cachexia. Studies published up to April 2023 were included. Important findings and study contributions were chosen and compiled using several databases including PubMed, Google Scholar, Science Direct, and ClinicalTrials.gov using relevant keywords. ResultsCancer cachexia is a complex disease involving multiple factors resulting in atrophy of skeletal muscles. Systemic inflammation, altered energy balance and carbohydrate metabolism, altered lipid and protein metabolism, and adipose tissue browning are some of the major culprits in cancer cachexia. Increased protein degradation and decreased protein synthesis lead to muscle atrophy. Changes in signaling pathway like ubiquitin-proteasome, autophagy, mTOR, AMPK, and IGF-1 also lead to muscle wasting. Physical exercise, nutritional supplementation, steroids, myostatin inhibitors, and interventions targeting on inflammation have been investigated to treat cancer cachexia. Some therapy showed positive results in preclinical and clinical settings, although more research on the efficacy and safety of the treatment should be done. ConclusionMuscle atrophy in cancer cachexia is the result of multiple complex mechanisms; as a result, a lot more research has been done to describe the pathophysiology of the disease. Targeted therapy and multimodal interventions can improve clinical outcomes for patients.

Automated summary

Cancer cachexia is a debilitating syndrome characterized by muscle atrophy and fat loss, caused by various mechanisms including the release of cytokines and the disruption of metabolic pathways. This review focuses on the imbalances in protein synthesis and degradation in skeletal muscles.