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The Biology of Cancer Cachexia and the Role of TNF-α

  • Chapter
Cytokines in the Genesis and Treatment of Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Cachexia, or wasting, is the most common syndrome resulting from human malignancies, estimated to contribute to nearly a quarter of all cancer deaths. Although cachexia has been clinically diagnosed for more than a century, it is only relatively recently that investigators have begun unraveling the molecular mechanisms underlying the wasting state that predominates in adipose and skeletal muscle tissues. Tumor necrosis factor-α, or TNF-α is considered a leading mediator or cancer cachexia. This cytokine is produced by tumor, immune, and stromal cells to provide a growth and survival advantage within the tumor microenvironment. It also functions in an autocrine and paracrine fashion in adipose and skeletal muscles to regulate tissue breakdown. TNF-induced fat catabolism is largely regulated through the feeding response and through the control of gene expression to differentiate and maintain the homeostasis of adipose tissue. Regulation of skeletal muscle catabolism in cachexia is regulated by the ubiquitin-proteasome system, whose activity may also be controlled by TNF. Elucidation of the TNF signaling pathway has provided further insight into the regulation of cancer cachexia. One effector of this pathway in particular, NF-kB, appears to be essential for TNF-mediated fat and skeletal muscle decay. Understanding the mechanisms by which NF-kB functions in cancer cachexia may reveal still other novel therapeutic targets of wasting that may be used in combination with currently existing anti-TNF therapy.

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Authors and Affiliations

  1. Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University College of Medicine, Columbus, OH

    Denis C. Guttridge PHD

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  1. Denis C. Guttridge PHD
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Editors and Affiliations

  1. The Ohio State University Comprehensive Cancer Center, Columbus, OH

    Michael A. Caligiuri MD

  2. University of Pittsburgh Cancer Center, Pittsburgh, PA

    Michael T. Lotze MD (Director) (Director)

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© 2007 Humana Press Inc.

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Guttridge, D.C. (2007). The Biology of Cancer Cachexia and the Role of TNF-α. In: Caligiuri, M.A., Lotze, M.T. (eds) Cytokines in the Genesis and Treatment of Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-455-1_16

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  • DOI: https://doi.org/10.1007/978-1-59745-455-1_16

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-820-2

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