IMR Press / FBL / Volume 13 / Issue 14 / DOI: 10.2741/3087

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

TNF: a moonlighting protein at the interface between cancer and infection
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1 Medical and Pharmaceutical Biotechnology, University of Applied Sciences, Krems, Austria
2 Vascular Biology Center, Medical College of Georgia, Augusta, GA, US
3 Institute of Physical Biology, USB and Institute of Systems Biology and Ecology , ASCR v.v.i., Nove Hrady, Czech Republic
4 Algonomics, Ghent, Belgium, University of Regensburg, Germany
5 Institute of Immunology, University of Regensburg, Germany
6 Biochemical Pharmacology, University of Konstanz, Germany

*Author to whom correspondence should be addressed.


Front. Biosci. (Landmark Ed) 2008, 13(14), 5374–5386;
Published: 1 May 2008

The remarkable ability of TNF, especially in combination with Interferon-gamma or melphalan, to inhibit the growth of malignant tumor cells is so far unmatched. Unfortunately, its high systemic toxicity and hepatotoxicity prevent its systemic use in cancer patients. An elegant manner to circumvent this problem is the isolated limb and liver perfusion for the treatment of melanoma, soft tissue sarcoma and liver tumors, respectively, although the latter method can lead to a reversible hepatotoxicity. In order to allow also the treatment of other cancers with TNF, new strategies have to be developed that aim at sensitizing tumor cells to TNF and at reducing its systemic and liver toxicity, without losing its antitumor efficiency. Moreover, the lectin-like domain of TNF, which is spatially distinct from the receptor binding sites, could be useful in reducing cancer treatment-related pulmonary edema formation. This review will discuss some recent developments in these areas, which can lead to a renewed interest in TNF for the systemic treatment of cancer.

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