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Pancreatic cancer cachexia: three dimensions of a complex syndrome

Abstract

Cancer cachexia is a multifactorial syndrome that is characterised by a loss of skeletal muscle mass, is commonly associated with adipose tissue wasting and malaise, and responds poorly to therapeutic interventions. Although cachexia can affect patients who are severely ill with various malignant or non-malignant conditions, it is particularly common among patients with pancreatic cancer. Pancreatic cancer often leads to the development of cachexia through a combination of distinct factors, which, together, explain its high prevalence and clinical importance in this disease: systemic factors, including metabolic changes and pathogenic signals related to the tumour biology of pancreatic adenocarcinoma; factors resulting from the disruption of the digestive and endocrine functions of the pancreas; and factors related to the close anatomical and functional connection of the pancreas with the gut. In this review, we conceptualise the various insights into the mechanisms underlying pancreatic cancer cachexia according to these three dimensions to expose its particular complexity and the challenges that face clinicians in trying to devise therapeutic interventions.

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Fig. 1: Conceptualisation of the three dimensions involved in the development of pancreatic cancer cachexia.
Fig. 2: Tumour-derived factors associated with cachexia in pancreatic adenocarcinoma.
Fig. 3: Impaired pancreatic exocrine and endocrine function interact with alterations in the digestive tract to promote pancreatic cancer cachexia.

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Acknowledgements

The authors would like to thank Rainer Heuchel for his critical comments and Erika Nieser for language editing.

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Conception and design: M.K. and J.M.L. Manuscript writing: M.K. and J.M.L. Final approval of manuscript: all authors. Accountable for all aspects of the work: all authors.

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M.K.: Alligator Bioscience (Consulting), Roche (Consulting); L.L.: no disclosures; L.E.: no disclosures; J.M.L.: Abbot (Honoraria), Mylan (Honoraria).

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This work was supported through a clinician-scientist grant from Region Stockholm to M.K. and the Lars Vesterlund minnesfond to J.M.L.

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Kordes, M., Larsson, L., Engstrand, L. et al. Pancreatic cancer cachexia: three dimensions of a complex syndrome. Br J Cancer 124, 1623–1636 (2021). https://doi.org/10.1038/s41416-021-01301-4

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