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Cancer cachexia: understanding the molecular basis

Nature Reviews Cancer volume 14, pages 754–762 (2014)Cite this article

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Abstract

Cancer cachexia is a devastating, multifactorial and often irreversible syndrome that affects around 50–80% of cancer patients, depending on the tumour type, and that leads to substantial weight loss, primarily from loss of skeletal muscle and body fat. Since cachexia may account for up to 20% of cancer deaths, understanding the underlying molecular mechanisms is essential. The occurrence of cachexia in cancer patients is dependent on the patient response to tumour progression, including the activation of the inflammatory response and energetic inefficiency involving the mitochondria. Interestingly, crosstalk between different cell types ultimately seems to result in muscle wasting. Some of the recent progress in understanding the molecular mechanisms of cachexia may lead to new therapeutic approaches.

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Figure 1: Main metabolic adaptations associated with tumour burden.
Figure 2: Skeletal muscle wasting during cachexia.
Figure 3: Browning of white adipose tissue in cachexia.
Figure 4: Cachexia as a multi-organ syndrome.

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Acknowledgements

This work was supported by a grant from the Ministerio de Ciencia yTecnología (SAF-26091-2011).

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Authors and Affiliations

  1. Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, 08028, Spain

    Josep M. Argilés, Sílvia Busquets & Francisco J. López-Soriano

  2. Institut de Biomedicina de la Universitat de Barcelona, Barcelona, 08028, Spain

    Josep M. Argilés, Sílvia Busquets & Francisco J. López-Soriano

  3. BS Nutrition Centre, Barcelona, 08195, Spain

    Britta Stemmler

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  1. Josep M. Argilés
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Correspondence to Josep M. Argilés.

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Competing interests

J.M.A.: Companies' Advisor 2003- Board of Advisors, Danone Research 2005- Board of Advisors, ANECA (National Agency for Evaluation of University Professors); also, on a non-regular basis, an advisor for: Novartis (Switzerland), Par Pharmaceuticals (USA), Sacoor Medical Group (UK), Amgen (USA) and Merck, Sharp and Dohme (USA), Abbott Pharmaceuticals (USA). S.B., B.S. and F.J.L.-S. declare no competing interests.

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Glossary

Adipokines

Cytokines that are released by adipose tissue cells.

Asthenia

From the Greek, a stenos, meaning 'without force'; loss of muscle force.

Brown adipose tissue

(BAT; also known as brown fat). One of two types of fat or adipose tissue (the other being white adipose tissue (also known as white fat)) found in mammals. Its primary function is to generate body heat, being responsible for the so-called non-shivering thermogenesis.

Calcium release units

Specialized junctional domains of the sarcoplasmic reticulum that bear calcium release channels, also known as ryanoidine receptors.

Glycaemia

Blood glucose levels.

Ghrelin resistance

Reduced effects of ghrelin, in spite of high circulating levels of the molecule.

Myokines

Cytokines that are released by skeletal muscle.

Sarcomere

From the Greek sarx (flesh) and meros (part), it represents the basic muscle. Sarcomeres are composed of long, fibrous proteins that slide past each other when the muscles contract and relax.

Total parenteral nutrition

Intravenous artificial nutrition without oral ingestion.

White adipose tissue

(WAT; also known as white fat). WAT is used as a store of energy in the form of triacylglycerols. It may account for up to 25% of body weight in healthy humans.

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Argilés, J., Busquets, S., Stemmler, B. et al. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer 14, 754–762 (2014). https://doi.org/10.1038/nrc3829

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