Deliberation on debilitating condition of cancer cachexia: Skeletal muscle wasting

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2023-07-20 DOI:10.1111/fcp.12931

Srusti Dave, Bhoomika M. Patel

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Abstract

Background

Cancer 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.

Objectives

This study aimed to elucidate the mechanisms involved in skeletal muscle wasting phenomenon over the last few years.

Methods

This 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.

Results

Cancer 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.

Conclusion

Muscle 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.

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对癌症恶病质衰弱状态的思考:骨骼肌萎缩。

背景:癌症恶病质是一种衰弱综合征，与肌肉萎缩和脂肪减少引起的显著体损相关。恶病质的发病机制有多种。肿瘤的存在释放炎症细胞和免疫细胞的细胞因子，这些细胞因子在激活和灭活与蛋白质、碳水化合物和脂质代谢相关的某些途径中起着重要作用。本文综述了骨骼肌中涉及蛋白质合成和降解失衡的各种级联反应。目的:本研究旨在阐明近年来骨骼肌萎缩现象的机制。方法:本文简要综述了癌症恶病质中肌肉萎缩的不同途径。纳入了截至2023年4月发表的研究。重要的发现和研究成果是通过PubMed、谷歌Scholar、Science Direct和ClinicalTrials.gov等多个数据库，使用相关关键词进行筛选和汇编的。结果:癌症恶病质是一种涉及多种因素导致骨骼肌萎缩的复杂疾病。全身炎症、能量平衡和碳水化合物代谢的改变、脂质和蛋白质代谢的改变以及脂肪组织褐变是癌症恶病质的一些主要罪魁祸首。蛋白质降解增加和蛋白质合成减少导致肌肉萎缩。泛素-蛋白酶体、自噬、mTOR、AMPK、IGF-1等信号通路的改变也会导致肌肉萎缩。体育锻炼、营养补充、类固醇、肌肉生长抑制素抑制剂和针对炎症的干预措施已被研究用于治疗癌症恶病质。一些治疗在临床前和临床环境中显示出积极的结果，尽管还需要对治疗的有效性和安全性进行更多的研究。结论:肿瘤恶病质肌萎缩是多种复杂机制的结果;因此，人们做了更多的研究来描述这种疾病的病理生理学。靶向治疗和多模式干预可以改善患者的临床结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.