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Understanding the mechanisms and treatment options in cancer cachexia

Abstract

Cancer cachexia is a metabolic syndrome that can be present even in the absence of weight loss ('precachexia'). Cachexia is often compounded by pre-existing muscle loss, and is exacerbated by cancer therapy. Furthermore, cachexia is frequently obscured by obesity, leading to under-diagnosis and excess mortality. Muscle wasting (the signal event in cachexia) is associated not only with reduced quality of life, but also markedly increased toxicity from chemotherapy. Many of the primary events driving cachexia are likely mediated via the central nervous system and include inflammation-related anorexia and hypoanabolism or hypercatabolism. Treatment of cachexia should be initiated early. In addition to active management of secondary causes of anorexia (such as pain and nausea), therapy should target reduced food intake (nutritional support), inflammation-related metabolic change (anti-inflammatory drugs or nutrients) and reduced physical activity (resistance exercise). Advances in the understanding of the molecular biology of the brain, immune system and skeletal muscle have provided novel targets for the treatment of cachexia. The combination of therapies into a standard multimodal package coupled with the development of novel therapeutics promises a new era in supportive oncology whereby quality of life and tolerance to cancer therapy could be improved considerably.

Key Points

  • Cancer cachexia remains an important unmet medical need that affects patients' quality of life and treatment outcomes

  • Cachexia can be missed in an ever-increasingly obese population

  • Therapy should start early and can run in parallel with antineoplastic therapy

  • There is an urgent need to establish best supportive multimodal care for cachexia: beyond good clinical or oncological care, the treatable defects in dietary intake, physical activity and systemic inflammation should be addressed

  • Patients with cachexia should be actively considered for entry into clinical trials

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Figure 1: Dual contribution of metabolic change and reduced food intake to cachexia.
Figure 2: Extensive muscle wasting can be obscured by large fat mass.
Figure 3: Threshold definition for sarcopenia: a low level of muscle, characterized by a statistically significant increase in health risk.
Figure 4: Integration of fuel metabolism in the tumour-bearing state.
Figure 5: Muscle-cell proliferation and protein synthesis in response to growth factors and amino acids can be impaired by targeted cancer therapies.
Figure 6: Main targets for anticachexia treatments are those factors with an immediate effect on the development and aggravation of cachexia.

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All authors researched data for the article, made a substantial contribution to the discussion of the content, wrote the manuscript, and reviewed and edited it prior to submission.

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Correspondence to Kenneth Fearon.

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K. Fearon acts either a consultant for or receives honoraria or research support from Abbott, Alder Biopharmaceuticals, Nutricia and Novartis. J. Arends receives honoraria or research support from Abbott, Baxter, B. Braun, Fresenius-Kabi and Nutricia. V. Baracos declares no competing interests.

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Fearon, K., Arends, J. & Baracos, V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 10, 90–99 (2013). https://doi.org/10.1038/nrclinonc.2012.209

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