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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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.
The authors declare no competing interests.
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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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