Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12:31–46.
Peng F, Liao M, Qin R, Zhu S, Peng C, Fu L, et al. Regulated cell death (RCD) in cancer: key pathways and targeted therapies. Signal Transduct Target Ther. 2022;7:286.
CAS PubMed PubMed Central Google Scholar
Newton K, Strasser A, Kayagaki N, Dixit VM. Cell death. Cell. 2024;187:235–56.
Christgen S, Tweedell RE, Kanneganti T-D. Programming inflammatory cell death for therapy. Pharmacol Ther. 2022;232:108010.
Rogers C, Fernandes-Alnemri T, Mayes L, Alnemri D, Cingolani G, Alnemri ES. Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat Commun. 2017;8:14128.
CAS PubMed PubMed Central Google Scholar
Gao W, Wang X, Zhou Y, Wang X, Yu Y. Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy. Signal Transduct Target Ther. 2022;7:196.
PubMed PubMed Central Google Scholar
Tong X, Tang R, Xiao M, Xu J, Wang W, Zhang B, et al. Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research. J Hematol Oncol. 2022;15:174.
PubMed PubMed Central Google Scholar
Wei X, Xie F, Zhou X, Wu Y, Yan H, Liu T, et al. Role of pyroptosis in inflammation and cancer. Cell Mol Immunol. 2022;19:971–92.
CAS PubMed PubMed Central Google Scholar
Carneiro BA, El-Deiry WS. Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol. 2020;17:395–417.
PubMed PubMed Central Google Scholar
Malireddi RKS, Kesavardhana S, Kanneganti T-D. ZBP1 and TAK1: master regulators of NLRP3 inflammasome/pyroptosis, apoptosis, and necroptosis (PAN-optosis). Front Cell Infect Microbiol. 2019;9:406.
CAS PubMed PubMed Central Google Scholar
Kuriakose T, Man SM, Malireddi RKS, Karki R, Kesavardhana S, Place DE, et al. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci Immunol. 2016;1:aag2045.
Pandian N, Kanneganti T-D. PANoptosis: a unique innate immune inflammatory cell death modality. J Immunol. 2022;209:1625–33.
Lin J-F, Hu P-S, Wang Y-Y, Tan Y-T, Yu K, Liao K, et al. Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis. Signal Transduct Target Ther. 2022;7:54.
CAS PubMed PubMed Central Google Scholar
Lee S, Karki R, Wang Y, Nguyen LN, Kalathur RC, Kanneganti T-D. AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature. 2021;597:415–9.
CAS PubMed PubMed Central Google Scholar
Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell. 2021;184:149–68.
Lin C, Lin P, Yao H, Liu S, Lin X, He R, et al. Modulation of YBX1-mediated PANoptosis inhibition by PPM1B and USP10 confers chemoresistance to oxaliplatin in gastric cancer. Cancer Lett. 2024;587:216712.
Tan Y-T, Li T, Wang R-B, Liu Z-K, Ma M-Y, Huang R-Z, et al. WTAP weakens oxaliplatin chemosensitivity of colorectal cancer by preventing PANoptosis. Cancer Lett. 2024;604:217254.
Zhang Z, Zhang F, Pang P, Li Y, Chen X, Sun S, et al. Identification of PANoptosis-relevant subgroups to evaluate the prognosis and immune landscape of patients with liver hepatocellular carcinoma. Front Cell Dev Biol. 2023;11:1210456.
PubMed PubMed Central Google Scholar
Wang X, Sun R, Chan S, Meng L, Xu Y, Zuo X, et al. PANoptosis-based molecular clustering and prognostic signature predicts patient survival and immune landscape in colon cancer. Front Genet. 2022;13:955355.
CAS PubMed PubMed Central Google Scholar
Yi X, Li J, Zheng X, Xu H, Liao D, Zhang T, et al. Construction of PANoptosis signature: novel target discovery for prostate cancer immunotherapy. Mol Ther Nucleic Acids. 2023;33:376–90.
CAS PubMed PubMed Central Google Scholar
Hänggi K, Li J, Gangadharan A, Liu X, Celias DP, Osunmakinde O, et al. Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity. Cancer Cell. 2024;42:2015–31.
Wang X, Guo X, Ren H, Song X, Chen L, Yu L, et al. An “Outer Piezoelectric and Inner Epigenetic” logic-gated PANoptosis for osteosarcoma sono-immunotherapy and bone regeneration. Adv Mater. 2025;37:e2415814.
Oh S, Lee J, Oh J, Yu G, Ryu H, Kim D, et al. Integrated NLRP3, AIM2, NLRC4, Pyrin inflammasome activation and assembly drive PANoptosis. Cell Mol Immunol. 2023;20:1513–26.
CAS PubMed PubMed Central Google Scholar
Zhang T, Yin C, Fedorov A, Qiao L, Bao H, Beknazarov N, et al. ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis. Nature. 2022;606:594–602.
CAS PubMed PubMed Central Google Scholar
Christgen S, Zheng M, Kesavardhana S, Karki R, Malireddi RKS, Banoth B, et al. Identification of the PANoptosome: a molecular platform triggering pyroptosis, apoptosis, and necroptosis (PANoptosis). Front Cell Infect Microbiol. 2020;10:237.
CAS PubMed PubMed Central Google Scholar
Karki R, Sharma BR, Lee E, Banoth B, Malireddi RKS, Samir P, et al. Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer. JCI Insight. 2020;5:e136720.
Kuriakose T, Kanneganti T-D. ZBP1: innate sensor regulating cell death and inflammation. Trends Immunol. 2018;39:123–34.
Liu K, Wang M, Li D, Duc Duong NT, Liu Y, Ma J, et al. PANoptosis in autoimmune diseases interplay between apoptosis, necrosis, and pyroptosis. Front Immunol. 2024;15:1502855.
CAS PubMed PubMed Central Google Scholar
Kesavardhana S, Malireddi RKS, Burton AR, Porter SN, Vogel P, Pruett-Miller SM, et al. The Zα2 domain of ZBP1 is a molecular switch regulating influenza-induced PANoptosis and perinatal lethality during development. J Biol Chem. 2020;295:8325–30.
CAS PubMed PubMed Central Google Scholar
Zhan J, Wang J, Liang Y, Wang L, Huang L, Liu S, et al. Apoptosis dysfunction: unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses. Cell Commun Signal. 2024;22:149.
CAS PubMed PubMed Central Google Scholar
Karki R, Lee S, Mall R, Pandian N, Wang Y, Sharma BR, et al. ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. Sci Immunol. 2022;7:eabo6294.
Lou J, Mao Y, Jiang W, Shen H, Fan Y, Yu Q, et al. TRIM56 modulates YBX1 degradation to ameliorate ZBP1-mediated neuronal PANoptosis in spinal cord injury. Adv Sci. 2024;11:e2407132.
Li J, Jia Y-C, Lu J, Zhang H, Wang Z, Xie X, et al. Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis. Cell Death Discov. 2025;11:180.
CAS PubMed PubMed Central Google Scholar
Bürckstümmer T, Baumann C, Blüml S, Dixit E, Dürnberger G, Jahn H, et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol. 2009;10:266–72.
Ma C, Li S, Hu Y, Ma Y, Wu Y, Wu C, et al. AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis. J Exp Med. 2021;218:e20201796.
Coll RC, Schroder K. Inflammasome components as new therapeutic targets in inflammatory disease. Nat Rev Immunol. 2025;25:22–41.
Cassel SL, Joly S, Sutterwala FS. The NLRP3 inflammasome: a sensor of immune danger signals. Semin Immunol. 2009;21:194–8.
CAS PubMed PubMed Central Google Scholar
Liu Y, Zhai H, Alemayehu H, Boulanger J, Hopkins LJ, Borgeaud AC, et al. Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization. Nat Commun. 2023;14:7246.
CAS PubMed PubMed Central Google Scholar
Paik S, Kim JK, Shin HJ, Park E-J, Kim IS, Jo E-K. Updated insights into the molecular networks for NLRP3 inflammasome activation. Cell Mol Immunol. 2025;22:563–96.
CAS PubMed PubMed Central Google Scholar
Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol. 2009;183:787–91.
Comments (0)