Cancer cachexia: molecular mechanisms and treatment strategies

Abstract

Muscle wasting is a consequence of physiological changes or a pathology characterized by increased catabolic activity that leads to progressive loss of skeletal muscle mass and strength. Numerous diseases, including cancer, organ failure, infection, and aging-associated diseases, are associated with muscle wasting. Cancer cachexia is a multifactorial syndrome characterized by loss of skeletal muscle mass, with or without the loss of fat mass, resulting in functional impairment and reduced quality of life. It is caused by the upregulation of systemic inflammation and catabolic stimuli, leading to inhibition of protein synthesis and enhancement of muscle catabolism. Here, we summarize the complex molecular networks that regulate muscle mass and function. Moreover, we describe complex multi-organ roles in cancer cachexia. Although cachexia is one of the main causes of cancer-related deaths, there are still no approved drugs for cancer cachexia. Thus, we compiled recent ongoing pre-clinical and clinical trials and further discussed potential therapeutic approaches for cancer cachexia.

Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach

“…The SwissTargetPrediction tool was used to determine the human targets of selected phytocompounds, and canonical SMILES were given as an input ( , accessed on 21 August 2023) [ 92 ]. In addition, 238 reported cachexia-associated genes were collected through a literature survey and web search for manual comparative analysis to find the unique genes [ 93 , 94 , 95 , 96 ]. The list of cachexia-associated genes collected is given in Supplementary Table S3 .…”

Toward a holistic understanding of cancer cachexia: Application of the human response to illness model

“… 19 While early explanations for the weight loss seen in patients with cancer was attributed to inadequate caloric intake, research has revealed that cachexia is in fact a complex systemic disease, characterized by tumor–host interactions, metabolic aberrations that result in negative energy balance, increased lean muscle proteolysis and adipose lipolysis, and neurohormonal dysregulation. 20 , 21 …”

“…Cytokines are regulatory proteins released by cells of the immune system and act asintercellular mediators in the generation of an immune response. 21 Upregulation of proinflammatory cytokines are implicated in altered metabolism and increased energy expenditure. Studies have demonstrated disturbances in REE in cancer patients such that even at rest, compared to healthy controls, cancer patients have increased rates of REE.…”

Comparison of the pharmacokinetic characteristics and bioequivalence between two nanosuspension formulations of megestrol acetate in healthy Korean male subjects

“…Cachexia refers to a phenomenon in which despite the intake of sufficient calories, there is a decrease in body weight, loss of appetite, or an imbalance in effects. The metabolic changes triggered by cancer cachexia, such as autophagy, elevated energy expenditure, nutrient sequestration by tumors, and proteolysis, collectively result in reduced oxidative capacity of cardiac muscle, disrupted mitochondrial homeostasis, and muscle atrophy, ultimately culminating in weight loss [ 1 ]. Cancer cachexia is multifactorial and cannot be fully reversed by nutritional support.…”