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Topics {✒️}

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Questions {❓}

• Cancer and necroptosis: friend or foe?
• Smac mimetics and TNFα: a dangerous liaison?

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WebPage:
      mainEntity:
         headline:The role of necroptosis in cancer biology and therapy
         description:Apoptosis resistance is to a large extent a major obstacle leading to chemotherapy failure during cancer treatment. Bypassing the apoptotic pathway to induce cancer cell death is considered to be a promising approach to overcoming this problem. Necroptosis is a regulated necrotic cell death modality in a caspase-independent fashion and is mainly mediated by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL). Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis resistance and may trigger and amplify antitumor immunity in cancer therapy. The role of necroptosis in cancer is complicated. The expression of key regulators of the necroptotic pathway is generally downregulated in cancer cells, suggesting that cancer cells may also evade necroptosis to survive; however, in certain types of cancer, the expression level of key mediators is elevated. Necroptosis can elicit strong adaptive immune responses that may defend against tumor progression; however, the recruited inflammatory response may also promote tumorigenesis and cancer metastasis, and necroptosis may generate an immunosuppressive tumor microenvironment. Necroptosis also reportedly promotes oncogenesis and cancer metastasis despite evidence demonstrating its antimetastatic role in cancer. In addition, necroptotic microenvironments can direct lineage commitment to determine cancer subtype development in liver cancer. A plethora of compounds and drugs targeting necroptosis exhibit potential antitumor efficacy, but their clinical feasibility must be validated. Better knowledge of the necroptotic pathway mechanism and its physiological and pathological functions is urgently required to solve the remaining mysteries surrounding the role of necroptosis in cancer. In this review, we briefly introduce the molecular mechanism and characteristics of necroptosis, the interplay between necroptosis and other cell death mechanisms, crosstalk of necroptosis and metabolic signaling and detection methods. We also summarize the intricate role of necroptosis in tumor progression, cancer metastasis, prognosis of cancer patients, cancer immunity regulation, cancer subtype determination and cancer therapeutics.
         datePublished:2019-05-23T00:00:00Z
         dateModified:2019-05-23T00:00:00Z
         pageStart:1
         pageEnd:17
         license:http://creativecommons.org/publicdomain/zero/1.0/
         sameAs:https://doi.org/10.1186/s12943-019-1029-8
         keywords:
            Necroptosis
            Autophagy
            Apoptosis
            Receptor-interacting protein kinase (RIPK)
            Mixed lineage kinase domain-like pseudokinase (MLKL)
            Metastasis
            Immunosuppression
            Therapeutics
            Cancer Research
            Oncology
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs12943-019-1029-8/MediaObjects/12943_2019_1029_Fig1_HTML.png
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs12943-019-1029-8/MediaObjects/12943_2019_1029_Fig2_HTML.png
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            name:Molecular Cancer
            issn:
               1476-4598
            volumeNumber:18
            type:
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         publisher:
            name:BioMed Central
            logo:
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               type:ImageObject
            type:Organization
         author:
               name:Yitao Gong
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                     name:Fudan University Shanghai Cancer Center
                     address:
                        name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                        type:PostalAddress
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                     name:Shanghai Medical College, Fudan University
                     address:
                        name:Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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                        name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
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                     name:Shanghai Medical College, Fudan University
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               name:Chao Yang
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               name:Quanxing Ni
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               name:Xianjun Yu
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                        type:PostalAddress
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               name:Chen Liu
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                     address:
                        name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                        type:PostalAddress
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                     name:Shanghai Medical College, Fudan University
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                        name:Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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                     name:Shanghai Pancreatic Cancer Institute
                     address:
                        name:Shanghai Pancreatic Cancer Institute, Shanghai, China
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ScholarlyArticle:
      headline:The role of necroptosis in cancer biology and therapy
      description:Apoptosis resistance is to a large extent a major obstacle leading to chemotherapy failure during cancer treatment. Bypassing the apoptotic pathway to induce cancer cell death is considered to be a promising approach to overcoming this problem. Necroptosis is a regulated necrotic cell death modality in a caspase-independent fashion and is mainly mediated by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL). Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis resistance and may trigger and amplify antitumor immunity in cancer therapy. The role of necroptosis in cancer is complicated. The expression of key regulators of the necroptotic pathway is generally downregulated in cancer cells, suggesting that cancer cells may also evade necroptosis to survive; however, in certain types of cancer, the expression level of key mediators is elevated. Necroptosis can elicit strong adaptive immune responses that may defend against tumor progression; however, the recruited inflammatory response may also promote tumorigenesis and cancer metastasis, and necroptosis may generate an immunosuppressive tumor microenvironment. Necroptosis also reportedly promotes oncogenesis and cancer metastasis despite evidence demonstrating its antimetastatic role in cancer. In addition, necroptotic microenvironments can direct lineage commitment to determine cancer subtype development in liver cancer. A plethora of compounds and drugs targeting necroptosis exhibit potential antitumor efficacy, but their clinical feasibility must be validated. Better knowledge of the necroptotic pathway mechanism and its physiological and pathological functions is urgently required to solve the remaining mysteries surrounding the role of necroptosis in cancer. In this review, we briefly introduce the molecular mechanism and characteristics of necroptosis, the interplay between necroptosis and other cell death mechanisms, crosstalk of necroptosis and metabolic signaling and detection methods. We also summarize the intricate role of necroptosis in tumor progression, cancer metastasis, prognosis of cancer patients, cancer immunity regulation, cancer subtype determination and cancer therapeutics.
      datePublished:2019-05-23T00:00:00Z
      dateModified:2019-05-23T00:00:00Z
      pageStart:1
      pageEnd:17
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12943-019-1029-8
      keywords:
         Necroptosis
         Autophagy
         Apoptosis
         Receptor-interacting protein kinase (RIPK)
         Mixed lineage kinase domain-like pseudokinase (MLKL)
         Metastasis
         Immunosuppression
         Therapeutics
         Cancer Research
         Oncology
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs12943-019-1029-8/MediaObjects/12943_2019_1029_Fig1_HTML.png
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs12943-019-1029-8/MediaObjects/12943_2019_1029_Fig2_HTML.png
      isPartOf:
         name:Molecular Cancer
         issn:
            1476-4598
         volumeNumber:18
         type:
            Periodical
            PublicationVolume
      publisher:
         name:BioMed Central
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Yitao Gong
            affiliation:
                  name:Fudan University Shanghai Cancer Center
                  address:
                     name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Shanghai Medical College, Fudan University
                  address:
                     name:Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Shanghai Pancreatic Cancer Institute
                  address:
                     name:Shanghai Pancreatic Cancer Institute, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Pancreatic Cancer Institute, Fudan University
                  address:
                     name:Pancreatic Cancer Institute, Fudan University, Shanghai, China
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Zhiyao Fan
            affiliation:
                  name:Fudan University Shanghai Cancer Center
                  address:
                     name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Shanghai Medical College, Fudan University
                  address:
                     name:Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
                     type:PostalAddress
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                  name:Shanghai Pancreatic Cancer Institute
                  address:
                     name:Shanghai Pancreatic Cancer Institute, Shanghai, China
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                  address:
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            name:Qiuyi Huang
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                  address:
                     name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                     type:PostalAddress
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                  name:Shanghai Medical College, Fudan University
                  address:
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                  name:Shanghai Pancreatic Cancer Institute
                  address:
                     name:Shanghai Pancreatic Cancer Institute, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Pancreatic Cancer Institute, Fudan University
                  address:
                     name:Pancreatic Cancer Institute, Fudan University, Shanghai, China
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Kun Fan
            affiliation:
                  name:Fudan University Shanghai Cancer Center
                  address:
                     name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Shanghai Medical College, Fudan University
                  address:
                     name:Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
                     type:PostalAddress
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                  name:Shanghai Pancreatic Cancer Institute
                  address:
                     name:Shanghai Pancreatic Cancer Institute, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Pancreatic Cancer Institute, Fudan University
                  address:
                     name:Pancreatic Cancer Institute, Fudan University, Shanghai, China
                     type:PostalAddress
                  type:Organization
            type:Person
            name:He Cheng
            affiliation:
                  name:Fudan University Shanghai Cancer Center
                  address:
                     name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Shanghai Medical College, Fudan University
                  address:
                     name:Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Shanghai Pancreatic Cancer Institute
                  address:
                     name:Shanghai Pancreatic Cancer Institute, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Pancreatic Cancer Institute, Fudan University
                  address:
                     name:Pancreatic Cancer Institute, Fudan University, Shanghai, China
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Kaizhou Jin
            affiliation:
                  name:Fudan University Shanghai Cancer Center
                  address:
                     name:Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                     type:PostalAddress
                  type:Organization
                  name:Shanghai Medical College, Fudan University
                  address:
                     name:Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
                     type:PostalAddress
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                  name:Shanghai Pancreatic Cancer Institute
                  address:
                     name:Shanghai Pancreatic Cancer Institute, Shanghai, China
                     type:PostalAddress
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      name:Pancreatic Cancer Institute, Fudan University, Shanghai, China
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