Preclinical and clinical studies on cancer-associated cachexia

Abstract

BACKGROUND: Cancer cachexia is the wasting condition that is often seen in advanced stage cancer patients. This wasting is largely attributable to a systemic and progressive loss of skeletal muscle mass that greatly hinders performance of normal daily activities, resulting in reduced quality of life. Moreover, it negatively influences the prognosis of cancer patients. A general consensus in the field is that the loss of muscle mass is due both to an increase in protein degradation and a decrease in protein synthesis. Recent studies using preclinical models for studying cachexia have been useful in identifying the contribution of inflammatory cytokines (e.g. tumor necrosis factor-α and Interleukin-6), and myostatin receptors (e.g. the type IIB activin receptor) to cachexia development, and have led to several clinical trials. However, many questions remain about the molecular mechanisms thought to play a role in the development of cachexia.

METHODS: We conducted a literature search using search engines, such as PubMed and Google Scholar to identify publications within the cancer cachexia field.

RESULTS: We summarized our current knowledge of: 1) the driving mechanisms of cancer cachexia, 2) the preclinical models available for studying the condition, and 3) the findings of recent clinical trials.

CONCLUSION: Cancer cachexia is a complex and variable condition that currently has no standard effective therapeutic treatment. Further studies are desperately needed to better understand this condition and develop effective combination treatments for patients.

Keywords

cancer cachexia / muscle wasting / bodyweight loss / metabolic changes / increased protein degradation / decreased protein synthesis

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Acknowledgements

This work is directly supported by National Cancer Institute Grants CA163124 (Y. Shiozawa), Department of Defense (W81XWH-14-1-0403 and W81XWH-17-1-0541, Y. Shiozawa), the Wake Forest Baptist Comprehensive Cancer Center Internal Pilot Funding (Y. Shiozawa), and the Wake Forest School of Medicine Internal Pilot Funding (Y. Shiozawa). Y. Shiozawa is supported as the Translational Research Academy which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR001420. This work is also supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

Compliance with ethics guidelines

D. Brooke Widner, D. Clark Files, Kathryn E. Weaver, Yusuke Shiozawa declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed. This article does not contain any studies with human subjects performed by any of the authors.

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