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Strategies to Overcome TRAIL Resistance in Cancer

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Resistance to Immunotherapeutic Antibodies in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 2))

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Abstract

For decades the therapeutic induction of cell death in cancer cells represents one of the key goals of cancer therapies. However, since cancer cells have developed multiple mechanisms to resist cell death induction, we are still far from reaching this aim. In principle, the TRAIL receptor/ligand system represents a promising approach to selectively initiate cell death pathways in cancer cells and is amendable for therapeutic targeting. Therefore, further insights into the molecular mechanisms that regulate TRAIL signal transduction and the events that control sensitivity and resistance of human cancers towards TRAIL-mediated cell death are critical to exploit this approach for the treatment of human cancers.

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Abbreviations

5-FU:

5-fluorouracil

AML:

Acute myeloid leukemia

APAF:

Apoptotic protease activating factor

cFLIP:

FLICE-like inhibitory protein

DISC:

Death-inducing signaling complex

FADD:

Fas-associated death domain

IAP:

Inhibitor of apoptosis

MAPK:

Mitogen-activated protein kinase

TNF:

Tumor necrosis factor

LOH:

Loss of heterozygosity

NF-κB:

Nuclear factor kappa-B

TNFR:

TNF receptor

TRAIL:

Tumor-necrosis-factor-related apoptosis-inducing ligand

XIAP:

X-linked inhibitor of apoptosis protein

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Acknowledgments

The expert secretarial assistance of C Hugenberg is greatly appreciated. This work has been partially supported by grants from the Deutsche Forschungsgemeinschaft, the Ministerium für Bildung und Forschung (01GM1104C), European Community and IAP VII P7/32.

Conflicts of Interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstr. 3a, 60528, Frankfurt, Germany

    Simone Fulda

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  1. Simone Fulda
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Correspondence to Simone Fulda .

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Editors and Affiliations

  1. Molecular Genetics, University of California, Los Angeles Dept. Microbiology, Immunology &, Los Angeles, California, USA

    Benjamin Bonavida

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Fulda, S. (2013). Strategies to Overcome TRAIL Resistance in Cancer. In: Bonavida, B. (eds) Resistance to Immunotherapeutic Antibodies in Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7654-2_8

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