Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Dec 4;21(23):9268.
doi: 10.3390/ijms21239268.

Cancer-Associated Muscle Wasting-Candidate Mechanisms and Molecular Pathways

Victoria S Armstrong  1   2 , Liam W Fitzgerald  1   2 , Oliver F Bathe  1   2   3
Affiliations
Review

Cancer-Associated Muscle Wasting-Candidate Mechanisms and Molecular Pathways

Victoria S Armstrong et al. Int J Mol Sci. .

Abstract

Excessive muscle loss is commonly observed in cancer patients and its association with poor prognosis has been well-established. Cancer-associated sarcopenia differs from age-related wasting in that it is not responsive to nutritional intervention and exercise. This is related to its unique pathogenesis, a result of diverse and interconnected mechanisms including inflammation, disordered metabolism, proteolysis and autophagy. There is a growing body of evidence that suggests that the tumor is the driver of muscle wasting by its elaboration of mediators that influence each of these pro-sarcopenic pathways. In this review, evidence for these tumor-derived factors and putative mechanisms for inducing muscle wasting will be reviewed. Potential targets for future research and therapeutic interventions will also be reviewed.

Keywords: cancer; mediators; muscle wasting; pathophysiology; sarcopenia; tumor; tumor-derived.

PubMed Disclaimer

Conflict of interest statement

O.F.B. has received funding from Pfizer Inc. for research on cachexia.

Figures

Figure 1
Figure 1
General mechanisms contributing to the pathogenesis of muscle wasting.
Figure 2
Figure 2
Tumor-derived factors have been described that are pro-inflammatory in nature, target the central nervous system (CNS) and directly target muscle. Mediators in red are also known to encourage tumor growth.
See this image and copyright information in PMC

References

    1. Fearon K.C., Strasser F., Anker S.D., Bosaeus I., Bruera E., Fainsinger R.L., Jatoi A., Loprinzi C., Macdonald N., Mantovani G., et al. Definition and classification of cancer cachexia: An international consensus. Lancet Oncol. 2011;12:489–495. doi: 10.1016/S1470-2045(10)70218-7. - DOI - PubMed
    1. Prado C.M.M., Lieffers J.R., McCargar L.J., Reiman T., Sawyer M.B., Martin L., Baracos V.E. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: A population-based study. Lancet Oncol. 2008;9:629–635. doi: 10.1016/S1470-2045(08)70153-0. - DOI - PubMed
    1. Argilés J.M., Busquets S., Stemmler B., López-Soriano F.J. Cancer cachexia: Understanding the molecular basis. Nat. Rev. Cancer. 2014;14:754–762. doi: 10.1038/nrc3829. - DOI - PubMed
    1. Vagnildhaug O.M., Balstad T.R., Almberg S.S., Brunelli C., Knudsen A.K., Kaasa S., Thronaes M., Laird B., Solheim T.S. A cross-sectional study examining the prevalence of cachexia and areas of unmet need in patients with cancer. Support. Care Cancer. 2017;26:1871–1880. doi: 10.1007/s00520-017-4022-z. - DOI - PubMed
    1. Baracos V.E., Mazurak V., Bhullar A.S. Cancer cachexia is defined by an ongoing loss of skeletal muscle mass. Ann. Palliat. Med. 2019;8:3–12. doi: 10.21037/apm.2018.12.01. - DOI - PubMed