A comprehensive review of animal models for cancer cachexia: Implications for translational research

Li, Li; Wazir, Junaid; Huang, Zhiqiang; Wang, Yong; Wang, Hongwei

doi:10.1016/j.gendis.2023.101080

Cited by 6 publications

(1 citation statement)

References 124 publications

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“…However, current animal models fall short of fully representing these diverse clinical aspects. 104,105 Particularly in advanced lung cancers, anorexia emerges as a critical symptom of CC, leading to reduced food intake and exacerbating systemic metabolic issues. Unlike metabolic changes caused by starvation or malabsorption, cancer-induced anorexia presents unique challenges.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics‐driven discovery of therapeutic targets for cancer cachexia

Cui,

Li,

Huang

et al. 2024

J cachexia sarcopenia muscle

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Cancer cachexia (CC) is a devastating metabolic syndrome characterized by skeletal muscle wasting and body weight loss, posing a significant burden on the health and survival of cancer patients. Despite ongoing efforts, effective treatments for CC are still lacking. Metabolomics, an advanced omics technique, offers a comprehensive analysis of small‐molecule metabolites involved in cellular metabolism. In CC research, metabolomics has emerged as a valuable tool for identifying diagnostic biomarkers, unravelling molecular mechanisms and discovering potential therapeutic targets. A comprehensive search strategy was implemented to retrieve relevant articles from primary databases, including Web of Science, Google Scholar, Scopus and PubMed, for CC and metabolomics. Recent advancements in metabolomics have deepened our understanding of CC by uncovering key metabolic signatures and elucidating underlying mechanisms. By targeting crucial metabolic pathways including glucose metabolism, amino acid metabolism, fatty acid metabolism, bile acid metabolism, ketone body metabolism, steroid metabolism and mitochondrial energy metabolism, it becomes possible to restore metabolic balance and alleviate CC symptoms. This review provides a comprehensive summary of metabolomics studies in CC, focusing on the discovery of potential therapeutic targets and the evaluation of modulating specific metabolic pathways for CC treatment. By harnessing the insights derived from metabolomics, novel interventions for CC can be developed, leading to improved patient outcomes and enhanced quality of life.

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Section: Discussionmentioning

confidence: 99%

Metabolomics‐driven discovery of therapeutic targets for cancer cachexia

Cui,

Li,

Huang

et al. 2024

J cachexia sarcopenia muscle

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The TWEAK/Fn14 signaling promotes skeletal muscle wasting during cancer cachexia

Tomaz da Silva,

Roy,

Vuong

et al. 2024

Preprint

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Cachexia is an involuntary loss of body weight mostly due to skeletal muscle wasting. The proinflammatory cytokine TWEAK and its receptor Fn14 constitute a major signaling system that regulates skeletal muscle mass in diverse conditions. However, the role of TWEAK/Fn14 system in the regulation of skeletal muscle mass during cancer-induced cachexia remains poorly understood. In this study, we demonstrate that the levels of Fn14, but not TWEAK, are induced in skeletal muscle of multiple mouse models of cancer cachexia. Targeted deletion of Fn14 inhibits muscle wasting and gene expression of multiple components of the ER stress-induced unfolded protein response (UPR) in the KPC mouse model of pancreatic ductal adenocarcinoma (PDAC) cancer cachexia. The TWEAK/Fn14 signaling activates PERK and IRE1α arm of the UPR and inhibits protein synthesis in cultured primary myotubes. Inhibition of PERK using pharmacological or molecular approaches improves protein synthesis and inhibits atrophy in TWEAK-treated cultured myotubes. Silencing of Fn14 in KPC cells prior to their inoculation in pancreas of mice also attenuates tumor growth without having any significant effect on muscle atrophy. The knockdown of Fn14 inhibits proliferation, migration, and invasion of cultured KPC cells. Finally, our results demonstrate that targeted ablation of Fn14 also attenuates muscle atrophy in the Lewis lung carcinoma model of cancer cachexia. Altogether, our study provides initial evidence that the inhibition of TWEAK/Fn14 signaling can prevent tumor growth and skeletal muscle wasting during cancer-induced cachexia.

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Exploring heterogeneity: a dive into preclinical models of cancer cachexia

Morena,

Cabrera,

Greene

2024

American Journal of Physiology-Cell Physiology

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Cancer Cachexia (CC) is a multifactorial and complex syndrome experienced by up to 80% of cancer patients and implicated in ~40% of cancer-related deaths. Given its significant impact on patients' quality of life and prognosis, there has been a growing emphasis on elucidating the underlying mechanisms of CC using pre-clinical models. However, the mechanisms of cachexia appear to differ across several variables including tumor type and model and biologic variables such as sex. These differences may be exacerbated by variance in experimental approaches and data reporting. This review examines literature spanning from 2011 to March 2024, focusing on common pre-clinical models of CC, including Lewis Lung Carcinoma, pancreatic KPC, and colorectal colon-26 and Apcmin/+ models. Our analysis reveals considerable heterogeneity in phenotypic outcomes, and investigated mechanisms within each model, with particular attention to sex differences which may be exacerbated through methodological differences. While searching for unified mechanisms is critical, we posit that effective treatment approaches are likely to leverage the heterogeneity presented by the tumor and pertinent biological variables to direct specific interventions. In exploring this heterogeneity, it becomes critical to consider methodological and data reporting approaches to best inform further research.

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A comprehensive review of animal models for cancer cachexia: Implications for translational research

Cited by 6 publications

References 124 publications

Metabolomics‐driven discovery of therapeutic targets for cancer cachexia

Metabolomics‐driven discovery of therapeutic targets for cancer cachexia

The TWEAK/Fn14 signaling promotes skeletal muscle wasting during cancer cachexia

Exploring heterogeneity: a dive into preclinical models of cancer cachexia

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