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Therapeutic Targets of the TNF Superfamily pp 195–206Cite as

TRAIL and Other TRAIL Receptor Agonists as Novel Cancer Therapeutics

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 647))

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo2L, is a member of the TNF superfamily (TNFSF) of cytokines. TRAIL gained much attention during the past decade due to the demonstration of its therapeutic potential as a tumor-specific apoptosis inducer. TRAIL was identified as a protein with high homology to other members of the TNF cytokine family, especially to the ligand of Fas/Apo-1 (CD95), CD95L (FasL/APO-1L). TRAIL has been shown to induce apoptosis selectively in many tumor cell lines without affecting normal cells and tissues, making TRAIL itself as well as agonists of the two human receptors of TRAIL which can submit an apoptotic signal, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), promising novel biotherapeutics for cancer therapy. An increasing number of publications now shows that TRAIL resistance in primary human tumor cells will have to be overcome and that sensitization to TRAIL-induced apoptosis will be required in many cases. Therefore, it will also be instrumental to develop suitable diagnostic tests to identify patients who will benefit from TRAIL-based novel anticancer therapeutics and those who will not. Interestingly, the first clinical results even in monotherapy with TRAIL as well as various agonistic TRAIL receptor-specific antibodies have shown encouraging results. This chapter provides a compact overview on the biochemistry of the TRAIL/TRAIL-R system, the physiological role of TRAIL and its receptors and the results of clinical trials with TRAIL and various TRAIL-R agonistic antibodies.

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Authors and Affiliations

  1. Department of Immunology Division of Medicine, Imperial College London, London, UK

    Christina Falschlehner & Henning Walczak

  2. Internal Medicine, University of Heidelberg, Heidelberg, Germany

    Tom M. Ganten & Ronald Koschny

  3. Division of Apoptosis Regulation, German Cancer Research Center, Heidelberg, Germany

    Uta Schaefer

Authors
  1. Christina Falschlehner
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  2. Tom M. Ganten
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  3. Ronald Koschny
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  4. Uta Schaefer
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  5. Henning Walczak
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Editors and Affiliations

  1. Department of Preclinical Therapeutics, Seattle Genetics, Inc., Bothell, Washington, USA

    Iqbal S. Grewal PhD

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Falschlehner, C., Ganten, T.M., Koschny, R., Schaefer, U., Walczak, H. (2009). TRAIL and Other TRAIL Receptor Agonists as Novel Cancer Therapeutics. In: Grewal, I.S. (eds) Therapeutic Targets of the TNF Superfamily. Advances in Experimental Medicine and Biology, vol 647. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89520-8_14

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