Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.

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2015

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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2015.08.031

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info:eu-repo/semantics/altIdentifier/pmid/26359988

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info:eu-repo/semantics/altIdentifier/eissn/1097-4172

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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_315D44A92CD88

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A.J. Johnston et al., « Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival. », Serveur académique Lausannois, ID : 10.1016/j.cell.2015.08.031


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The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumor-induced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- and TWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients.

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