Musculoskeletal fatigue in cancer patients with cachexia: A systematic review
Keywords:
cancer, cachexia, musculoskeletal fatigueAbstract
Background: Cachexia is a multifactorial syndrome commonly seen in cancer patients, marked by significant weight and muscle loss, and is strongly associated with cancer-related fatigue (CRF). This condition results from an imbalance in muscle protein homeostasis, exacerbated by systemic inflammation and metabolic dysregulation. Understanding the relationship between muscle wasting and fatigue in cachexia can provide insights into potential therapeutic interventions.
Methods: A systematic review was conducted using databases such as PubMed, ScienceDirect, and EMBASE. Keywords included “cachexia,” “cancer,” “biomarker,” and “fatigue.” Inclusion criteria were studies involving cancer patients with cachexia, with fatigue as a primary outcome and musculoskeletal system biomarkers as key variables. After screening 3,434 articles, two studies met the inclusion criteria.
Results: Both studies emphasized the critical role of muscle mass and strength in fatigue. The first study demonstrated significant negative correlations between handgrip strength (HGS), quadriceps strength (QS), skeletal muscle mass index (SMMI), and fatigue levels (measured by the Brief Fatigue Inventory, BFI) in male patients, suggesting muscle wasting as a primary contributor to fatigue. The second study (n=83) found no significant associations between fatigue and inflammatory cytokines such as IL-1b, IL-6, IL-8, and TNF-α, challenging the conventional view of inflammation as the primary driver of fatigue in cachexia.
Discussion: The findings highlight muscle bioenergetic inefficiency and metabolic disturbances as key mechanisms underlying fatigue in cancer cachexia, with inflammatory pathways playing a less significant role. Gender differences in musculoskeletal markers’ influence on fatigue underscore the need for tailored interventions.
Conclusion: Muscle wasting is a central determinant of fatigue in cancer cachexia, while the role of inflammation remains inconclusive. Further research is essential to explore alternative mechanisms and develop targeted therapies.
References
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.
Nagai H, Kim YH. Cancer prevention from the perspective of global cancer burden patterns. J Thorac Dis. 2017;9(3):448.
Baracos VE, Martin L, Korc M, Guttridge DC, Fearon KCH. Cancer-associated cachexia. Nat Rev Dis Primers. 2018;4(1):1–18.
Henson LA, Maddocks M, Evans C, Davidson M, Hicks S, Higginson IJ. Palliative care and the management of common distressing symptoms in advanced cancer: pain, breathlessness, nausea and vomiting, and fatigue. Journal of clinical oncology. 2020;38(9):905–14.
Webster JM, Kempen LJAP, Hardy RS, Langen RCJ. Inflammation and skeletal muscle wasting during cachexia. Front Physiol. 2020;11:597675.
Haberecht-Müller S, Krüger E, Fielitz J. Out of control: the role of the ubiquitin proteasome system in skeletal muscle during inflammation. Biomolecules. 2021;11(9):1327.
Ji LL, Yeo D. Mitochondrial dysregulation and muscle disuse atrophy. F1000Res. 2019;8.
Kilgour RD, Vigano A, Trutschnigg B, Hornby L, Lucar E, Bacon SL, et al. Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer. J Cachexia Sarcopenia Muscle. 2010;1:177–85.
Ma JF, Sanchez BJ, Hall DT, Tremblay AK, Di Marco S, Gallouzi I. STAT 3 promotes IFN γ/TNF α‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner. EMBO Mol Med. 2017;9(5):622–37.
Dodson S, Baracos VE, Jatoi A, Evans WJ, Cella D, Dalton JT, et al. Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies. Annu Rev Med. 2011;62(1):265–79.
Aquila G, Re Cecconi AD, Brault JJ, Corli O, Piccirillo R. Nutraceuticals and exercise against muscle wasting during cancer cachexia. Cells. 2020;9(12):2536.
Wang XS. Pathophysiology of cancer-related fatigue. Clin J Oncol Nurs. 2008;12(5 Suppl):11.
Scheede-Bergdahl C, Watt HL, Trutschnigg B, Kilgour RD, Haggarty A, Lucar E, et al. Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer cachexia? Clinical nutrition. 2012;31(1):85–8.
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95.
Argilés JM, Busquets S, Stemmler B, López-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754–62.
Fan W, Waizenegger W, Lin CS, Sorrentino V, He MX, Wall CE, et al. PPARδ promotes running endurance by preserving glucose. Cell Metab. 2017;25(5):1186–93.
Grossberg AJ, Vichaya EG, Gross PS, Ford BG, Scott KA, Estrada D, et al. Interleukin 6-independent metabolic reprogramming as a driver of cancer-related fatigue. Brain Behav Immun. 2020;88:230–41.
Cahill Jr GF. Fuel metabolism in starvation. Annu Rev Nutr. 2006;26(1):1–22.
Yang S, Chu S, Gao Y, Ai Q, Liu Y, Li X, et al. A narrative review of cancer-related fatigue (CRF) and its possible pathogenesis. Cells. 2019;8(7):738.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Tegar Fitriyana Sukaya Karso, Mas Rizky Anggun Syamsunarno, Irma Ruslina Defi
This work is licensed under a Creative Commons Attribution 4.0 International License.
OPEN ACCESS
All the articles of the European Journal of Oncology and Environmental Health are published with open access under the CC-BY Creative Commons attribution license (the current version is CC-BY, version 4.0 http://creativecommons.org/licenses/by/4.0/). This means that the author(s) retain copyright, but the content is free to download, distribute and adapt for commercial or non-commercial purposes, given appropriate attribution to the original article.
The articles in the previous edition of the Journal (European Journal of Oncology) are made available online with open access under the CC-BY Creative Commons attribution license (the current version is CC-BY, version 4.0 http://creativecommons.org/licenses/by/4.0/).
Upon submission, author(s) grant the Journal the license to publish their original unpublished work within one year, and the non exclusive right to display, store, copy and reuse the content. The CC-BY Creative Commons attribution license enables anyone to use the publication freely, given appropriate attribution to the author(s) and citing the Journal as the original publisher. The CC-BY Creative Commons attribution license does not apply to third-party materials that display a copyright notice to prohibit copying. Unless the third-party content is also subject to a CC-BY Creative Commons attribution license, or an equally permissive license, the author(s) must comply with any third-party copyright notices.
How to Cite
