Review Article | Published:

Inter-tissue communication in cancer cachexia


Cachexia is a systemic condition that occurs during many neoplastic diseases, such as cancer. Cachexia in cancer is characterized by loss of body weight and muscle and by adipose tissue wasting and systemic inflammation. Cancer cachexia is often associated with anorexia and increased energy expenditure. Even though the cachectic condition severely affects skeletal muscle, a tissue that accounts for ~40% of total body weight, it represents a multi-organ syndrome that involves tissues and organs such as white adipose tissue, brown adipose tissue, bone, brain, liver, gut and heart. Indeed, evidence suggests that non-muscle tissues and organs, as well as tumour tissues, secrete soluble factors that act on skeletal muscle to promote wasting. In addition, muscle tissue also releases various factors that can interact with the metabolism of other tissues during cancer. In this Review, we examine the effect of non-muscle tissues and inter-tissue communication in cancer cachexia and discuss studies aimed at developing novel therapeutic strategies for the condition.

Key points

  • Cancer cachexia is an energy-wasting syndrome caused by decreased food intake (owing to marked anorexia) and increased energy expenditure.

  • Cancer cachexia affects many tissues, including adipose tissues, heart, bone, liver, gastrointestinal tract and brain.

  • Systemic inflammation is a hallmark of patients with cancer, and the inflammatory response is involved in the metabolic alterations present during cancer cachexia.

  • The balance between pro-cachectic cytokines and anti-cachectic cytokines, both of which are produced by many cell types, might actually determine the cachectic response.

  • The importance of the metabolic changes that occurr in white and brown adipose tissues during cancer cachexia have been underestimated.

  • We need to unravel the communication between skeletal muscle and other tissues to better understand the aetiology of cancer cachexia.

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The work of the authors is supported by a grant from the Ministerio de Ciencia y Tecnología (MCyT) (SAF2015-65589-P).

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All authors contributed equally to this work.

Competing interests

B.S. is an employee of BSA Nutrition Center, which is a non-academic, for-profit affiliation. The other authors declare no competing interests.

Correspondence to Silvia Busquets.

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Fig. 1: The multi-organ nature of cancer cachexia.
Fig. 2: Inter-organ communication influences metabolic homeostasis in cancer cachexia.