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Cancer-associated cachexia

Abstract

Cancer-associated cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake and metabolic changes, including elevated energy expenditure, excess catabolism and inflammation. Cachexia is highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver and bowel; this group of malignancies is responsible for half of all cancer deaths worldwide. Cachexia involves diverse mediators derived from the cancer cells and cells within the tumour microenvironment, including inflammatory and immune cells. In addition, endocrine, metabolic and central nervous system perturbations combine with these mediators to elicit catabolic changes in skeletal and cardiac muscle and adipose tissue. At the tissue level, mechanisms include activation of inflammation, proteolysis, autophagy and lipolysis. Cachexia associates with a multitude of morbidities encompassing functional, metabolic and immune disorders as well as aggravated toxicity and complications of cancer therapy. Patients experience impaired quality of life, reduced physical, emotional and social well-being and increased use of healthcare resources. To date, no effective medical intervention completely reverses cachexia and there are no approved drug therapies. Adequate nutritional support remains a mainstay of cachexia therapy, whereas drugs that target overactivation of catabolic processes, cell injury and inflammation are currently under investigation.

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Figure 1: Cancer cachexia by tumour site.
Figure 2: Severe muscle depletion can occur in patients with cachexia and/or obesity.
Figure 3: Interorgan relationships in cancer-associated cachexia.
Figure 4: Signalling pathways involved in tumour-induced skeletal muscle atrophy.
Figure 5: Grading scheme for WL on the basis of risk of mortality in patients with advanced-stage cancer.
Figure 6: Proportional distribution of therapeutic approaches in clinical trials of cancer-associated cachexia therapy.

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Acknowledgements

The authors thank R.J.E. Skipworth (University of Edinburgh) for his valuable input.

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Introduction (V.E.B.); Epidemiology (L.M.); Mechanisms/pathophysiology (M.K. and D.C.G.); Diagnosis, screening and prevention (V.E.B.); Management (K.C.H.F.); Quality of life (V.E.B.); Outlook (V.E.B.); and Overview of the Primer (V.E.B.).

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Correspondence to Vickie E. Baracos.

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Competing interests

V.E.B. receives financial support from the Canadian Institutes of Health Research and The Alberta Cancer Foundation. L.M. is funded by Alberta Innovates, the Izaak Walton Killam Foundation and the American Society of Parenteral and Enteral Nutrition. M.K. is partially funded by National Cancer Institute grant CA-075059 and by the consortium for the study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (U01 DK108323). D.C.G. receives funding support from the US NIH and from the Ohio State University Comprehensive Cancer Center.

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Baracos, V., Martin, L., Korc, M. et al. Cancer-associated cachexia. Nat Rev Dis Primers 4, 17105 (2018). https://doi.org/10.1038/nrdp.2017.105

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