AI Article Synopsis
- The cytokine TWEAK and its receptor Fn14 are linked to tumor growth and are elevated in cancer, leading to complications like cachexia (muscle and weight loss).
- Research showed that targeting Fn14 with antibodies can significantly increase lifespan in cancer patients by minimizing muscle and fat loss, even though it only moderately affects tumor size.
- Fn14's role in inducing cachexia is primarily through tumor signaling, as tumors in mice lacking Fn14 had similar cachexia symptoms to those with functional Fn14, suggesting Fn14 antibodies could be a valuable treatment for cachexia in cancer.
Article Abstract
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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| http://dx.doi.org/10.1016/j.cell.2015.08.031 | DOI Listing |
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