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Regulation of Death Receptor-Induced Apoptosis by NF-κB and Interferon Signaling Pathways

Implications for Cancer Therapy

  • Chapter
Death Receptors in Cancer Therapy

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

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Abstract

Programmed cell death, or apoptosis, enables the physiologic culling of excess cells during embryonic development as well as the selective attrition of cells for tissue remodeling, regeneration, and homeostasis. The vertebrate immune system uses apoptosis to delete lymphocytes with inoperative or auto-reactive receptors from its repertoire, and to reverse clonal expansion at the end of an immune response. Cytotoxic T-lymphocytes and natural killer (NK) cells induce apoptosis of target cells during innate and adaptive immune responses against intracellular pathogens, cancer cells, or transplanted tissues. The altruistic demise of cells in response to cellular stress or injury or genetic errors, serves to preserve genomic integrity and constitutes an important mechanism of tumor surveillance. Given the crucial role of apoptosis in such a diverse array of physiological functions, it is no surprise that aberrations of this process underlie a host of developmental, immune, degenerative, and neoplastic disorders. This appreciation has fuelled frenetic investigation of the molecular determinants and regulatory mechanisms of apoptosis (1). The molecular execution of cell death involves activation of members of a family of cysteine-dependent aspartate-specific proteases (caspases). One mechanism of activating caspases, termed the extrinsic pathway, is triggered by engagement of cell surface death receptors by their specific ligands (2). In this chapter, we review our current understanding of the molecular determinants of death receptor-induced apoptosis, and identify the key regulators of these death-signaling pathways. We also highlight the enormous promise of targeting death receptors or their regulatory circuits for treatment of human cancers.

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Authors and Affiliations

  1. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD

    Rajani Ravi PhD & Atul Bedi MD

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  1. Rajani Ravi PhD
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  2. Atul Bedi MD
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Editors and Affiliations

  1. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA

    Wafik S. El-Deiry MD, PhD

  2. Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA

    Wafik S. El-Deiry MD, PhD

  3. Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA

    Wafik S. El-Deiry MD, PhD

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© 2005 Humana Press Inc., Totowa, NJ

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Ravi, R., Bedi, A. (2005). Regulation of Death Receptor-Induced Apoptosis by NF-κB and Interferon Signaling Pathways. In: El-Deiry, W.S. (eds) Death Receptors in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-851-X:231

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  • DOI: https://doi.org/10.1385/1-59259-851-X:231

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-172-1

  • Online ISBN: 978-1-59259-851-9

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