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Therapeutic Targeting of TWEAK/Fn14 in Cancer: Exploiting the Intrinsic Tumor Cell Killing Capacity of the Pathway

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Death Receptors and Cognate Ligands in Cancer

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 49))

Abstract

TNF-like weak inducer of apoptosis (TWEAK) and FGF-inducible molecule 14 (Fn14) are a TNF superfamily ligand–receptor pair. Initially identified as an inducer of tumor cell killing, TWEAK has pleiotropic effects, mediating pro-inflammatory and pro-angiogenic activity as well as stimulation of invasion, migration, and survival through its widely recognized receptor, Fn14. Fn14 is expressed at relatively low levels in normal tissues, but is dramatically elevated locally in injured and diseased tissues, where it plays a role in tissue remodeling. Herein we review the link between the TWEAK/Fn14 pathway and cancer as well as discuss potential therapeutic strategies targeting this pathway for cancer treatment. Many of the activities associated with the TWEAK/Fn14 pathway are linked with tumorigenesis and could thereby provide a growth advantage to tumors, suggesting that inhibition of the pathway may be beneficial in the treatment of cancer. At the same time, the elevated expression of Fn14 by tumor cells as well as the intrinsic tumor cell killing capacity of this receptor represents a promising alternative of harnessing the intrinsic tumor cell killing capacity of Fn14 to treat cancer.

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Acknowledgments

We acknowledge our colleagues at Biogen Idec, who have contributed to our conceptual understanding of the TWEAK/Fn14 pathway in cancer and provided unpublished data to support our conclusions: Aldo Amatucci, Jeff Browning, Ellen Garber, Yen-Ming Hsu, Timothy Zheng, and the Oncopharmacology group.

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  1. Biogen Idec, 12 Cambridge Center, Cambridge, MA, 02142, USA

    Jennifer S. Michaelson & Linda C. Burkly

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  1. Jennifer S. Michaelson
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Correspondence to Jennifer S. Michaelson .

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  1. Klinik für Allgemeine Chirurgie und, Universitätsklinikum Schleswig-Holstein, Arnold-Heller-Str. 7, Kiel, 24105, Germany

    Holger Kalthoff

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Michaelson, J.S., Burkly, L.C. (2009). Therapeutic Targeting of TWEAK/Fn14 in Cancer: Exploiting the Intrinsic Tumor Cell Killing Capacity of the Pathway. In: Kalthoff, H. (eds) Death Receptors and Cognate Ligands in Cancer. Results and Problems in Cell Differentiation, vol 49. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2008_18

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