title: Cancer and necroptosis: friend or foe?
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.
authors.affiliation: Institut für Immunologie, Christian-Albrechts-Universität, Michaelisstraße 5, 24105, Kiel, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Philipp
authors.affiliation: Institut für Immunologie, Christian-Albrechts-Universität, Michaelisstraße 5, 24105, Kiel, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Sosna
authors.affiliation: Institut für Immunologie, Christian-Albrechts-Universität, Michaelisstraße 5, 24105, Kiel, Germany. dadam@email.uni-kiel.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Adam
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D009336:Necrosis / Q000473:pathology*; D009369:Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Cancer; Necroptosis; Regulated necrosis; TNF; TRAIL