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Pathophysiology of cancer cachexia

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Abstract

Patients with advanced cancer and cachexia typically demonstrate modestly increased rates of energy expenditure in the presence of diminished food intake due to anorexia and to gastrointestinal disturbances. Rates of glucose production by the liver, gluconeogenesis and glycolysis to lactate (Cori cycle) are increased, fat mobilisation and oxidation are accelerated. There is a redistribution of body proteins away from muscle towards visceral proteins, resulting in marked muscle protein loss. Cancer cachexia differs from simple starvation and demonstrates metabolic similarities to sepsis or polytrauma. The metabolic response in the patient with cancer is largely due to mediators released by the tumour or by the host; recently the role of cytokines such as tumour necrosis factor α (TNFα), interleukin-1 (IL-1) and-6 (IL-6) and interferon γ (INFγ) has been emphasized. Catabolic hormones such as glucocorticoids and adrenaline have also been implicated. Cytokines have the potential to reproduce experimentally the clinical syndrome of cancer cachexia. There is evidence of increased production of several of them in certain types of cancer. There are overlapping activities of the cytokines TNFα, IL-1, IFNγ and IL-6. The contribution of each of them to cancer cachexia remains unclear. Inhibition of cytokine activity using specific antibodies in cancer-bearing experimental animals demonstrated partial prevention of cachexia. A positive feedback between macrophage-derived IL-1 and tumour-derived IL-6 has been demonstrated recently in experimental cancer cachexia. Cytokines may support tumour growth by acting as growth factors.

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Authors and Affiliations

  1. Department of Internal Medicine, University Hospital, Petersgraben 4, CH-4031, Basel, Switzerland

    Ulrich Keller

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  1. Ulrich Keller
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Keller, U. Pathophysiology of cancer cachexia. Support Care Cancer 1, 290–294 (1993). https://doi.org/10.1007/BF00364965

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