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Understanding cachexia in the context of metastatic progression

Nature Reviews Cancer volume 20, pages 274–284 (2020)Cite this article

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Abstract

Tumours reprogram host physiology, metabolism and immune responses during cancer progression. The release of soluble factors, exosomes and metabolites from tumours leads to systemic changes in distant organs, where cancer cells metastasize and grow. These tumour-derived circulating factors also profoundly impact tissues that are rarely inhabited by metastatic cancer cells such as skeletal muscle and adipose tissue. In fact, the majority of patients with metastatic cancer develop a debilitating muscle-wasting syndrome, known as cachexia, that is associated with decreased tolerance to antineoplastic therapy, poor prognosis and accelerated death, with no approved treatments. In this Perspective, we discuss the development of cachexia in the context of metastatic progression. We briefly discuss how circulating factors either directly or indirectly promote cachexia development and examine how signals from the metastatic process can trigger and amplify this process. Finally, we highlight promising therapeutic opportunities for targeting cachexia in the context of metastatic cancers.

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Fig. 1: Common mechanisms of muscle atrophy in cancer independent of stage.
Fig. 2: Potential triggers of cachexia during pre-metastatic conditioning.
Fig. 3: Changes in metastatic microenvironments: amplifiers of cachexia?

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Acknowledgements

The authors thank W. Ma, M. Kluger, G. Karsenty (CUIMC) and G. Miller (NYU) for helpful discussions. Funding was received from NCI CA231239, Pershing Square Sohn Prize, Irving Scholar Award, Interdisciplinary Research Initiatives Seed (IRIS) program, Developmental funds from NIH/NCI Cancer Center Support Grant P30CA013696 and The Irma T. Hirschl Monique Weill-Caulier Trust Award to S.A.

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  1. Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, NY, USA

    Anup K. Biswas & Swarnali Acharyya

  2. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA

    Swarnali Acharyya

  3. Herbert Irving Comprehensive Cancer Center, New York, NY, USA

    Swarnali Acharyya

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Biswas, A.K., Acharyya, S. Understanding cachexia in the context of metastatic progression. Nat Rev Cancer 20, 274–284 (2020). https://doi.org/10.1038/s41568-020-0251-4

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