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Cancer and necroptosis: friend or foe?

  • Multi-author review
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Abstract

Regulated cell death is one major factor to ensure homoeostasis in multicellular organisms. For decades, apoptosis was considered as the sole form of regulated cell death, whereas necrosis was believed to be accidental and unregulated. Due to this view, research on necrosis was somewhat neglected, especially in the field of anti-cancer treatment. However, new interest in necrosis has been sparked by the recent discovery of different forms of necrosis that show indeed regulated pathways. More and more studies now address the molecular pathways of regulated necrosis and its connections within the cellular signaling networks. Necroptosis, a subform of regulated necrosis, has so far hardly been focused on with regard to a future treatment of cancer patients and may emerge as a novel and effective approach to eliminate tumor cells. However, and similar to apoptosis, tumor cells can develop resistances against necroptosis to ensure their own survival. In this context, new molecules that enhance necroptosis are currently being identified to overcome such resistances. This review discusses cancer and necroptosis as friends or foes, i.e. the options to exploit necroptosis in anti-cancer therapies (“foes”), but also potential limitations that may block or actually cause necroptosis to act in a protumoral manner (“friends”). The balance between these two possible roles will determine whether necroptosis can indeed be used as a promising tool for early diagnosis of tumors, prevention of metastasis and anti-cancer treatment.

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Acknowledgments

This work was supported by grants from the Deutsche Krebshilfe (110055) and the Deutsche Forschungsgemeinschaft (SFB 877, project B2 and Cluster of Excellence “Inflammation at Interfaces”, EXC306-PMTP1 and EXC306-PWTP2) to D. A. and a junior grant from the Medical Faculty of the Christian-Albrechts-University to S. P.

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    1. Institut für Immunologie, Christian-Albrechts-Universität, Michaelisstraße 5, 24105, Kiel, Germany

      Stephan Philipp, Justyna Sosna & Dieter Adam

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    1. Stephan Philipp
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    2. Justyna Sosna
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    Correspondence to Dieter Adam.

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    S. Philipp and J. Sosna contributed equally to this work.

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    Philipp, S., Sosna, J. & Adam, D. Cancer and necroptosis: friend or foe?. Cell. Mol. Life Sci. 73, 2183–2193 (2016). https://doi.org/10.1007/s00018-016-2193-2

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