EditorialEditorial
Open Access

Harnessing the STING pathway for HCC treatment

Carmen Chak-Lui Wong, Cerise Yuen-Ki Chan, Helen Do-Gai Xue and Chun-Ming Wong
Cancer Biology & Medicine December 2025, 22 (12) 1423-1430; DOI: https://doi.org/10.20892/j.issn.2095-3941.2025.0434

References

  1. 1.↵
    2. Lanng KRB,
    3. Lauridsen EL,
    4. Jakobsen MR.
    The balance of STING signaling orchestrates immunity in cancer. Nat Immunol. 2024; 25: 1144–57.
    OpenUrlCrossRefPubMed
  2. 2.↵
    2. Duan Y,
    3. Hu Z,
    4. Han P,
    5. Lei B,
    6. Wang S,
    7. Wang Z, et al.
    ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion. Nat Cell Biol. 2025; 27: 668–82.
    OpenUrlPubMed
  3. 3.↵
    2. Erdal E,
    3. Haider S,
    4. Rehwinkel J,
    5. Harris AL,
    6. McHugh PJ.
    A prosurvival DNA damage-induced cytoplasmic interferon response is mediated by end resection factors and is limited by Trex1. Genes Dev. 2017; 31: 353–69.
    OpenUrlAbstract/FREE Full Text
  4. 4.
    2. Guan J,
    3. Lu C,
    4. Jin Q,
    5. Lu H,
    6. Chen X,
    7. Tian L, et al.
    MLH1 deficiency-triggered DNA hyperexcision by exonuclease 1 activates the cGAS-STING pathway. Cancer Cell. 2021; 39: 109–21.e5.
    OpenUrlCrossRefPubMed
  5. 5.
    2. Hartlova A,
    3. Erttmann SF,
    4. Raffi FA,
    5. Schmalz AM,
    6. Resch U,
    7. Anugula S, et al.
    DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity. 2015; 42: 332–43.
    OpenUrlCrossRefPubMed
  6. 6.↵
    2. Ho SS,
    3. Zhang WY,
    4. Tan NY,
    5. Khatoo M,
    6. Suter MA,
    7. Tripathi S, et al.
    The DNA structure-specific endonuclease MUS81 mediates DNA sensor STING-dependent host rejection of prostate cancer cells. Immunity. 2016; 44: 1177–89.
    OpenUrlPubMed
  7. 7.↵
    2. Harding SM,
    3. Benci JL,
    4. Irianto J,
    5. Discher DE,
    6. Minn AJ,
    7. Greenberg RA.
    Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature. 2017; 548: 466–70.
    OpenUrlCrossRefPubMed
  8. 8.↵
    2. Ding L,
    3. Kim HJ,
    4. Wang Q,
    5. Kearns M,
    6. Jiang T,
    7. Ohlson CE, et al.
    PARP inhibition elicits STING-dependent antitumor immunity in Brca1-deficient ovarian cancer. Cell Rep. 2018; 25: 2972–80.e5.
    OpenUrlCrossRefPubMed
  9. 9.
    2. Pantelidou C,
    3. Sonzogni O,
    4. De Oliveria Taveira M,
    5. Mehta AK,
    6. Kothari A,
    7. Wang D, et al.
    PARP inhibitor efficacy depends on CD8+ T-cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer. Cancer Discov. 2019; 9: 722–37.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    2. Shen J,
    3. Zhao W,
    4. Ju Z,
    5. Wang L,
    6. Peng Y,
    7. Labrie M, et al.
    PARPi triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCAness. Cancer Res. 2019; 79: 311–9.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    2. Chen YA,
    3. Shen YL,
    4. Hsia HY,
    5. Tiang YP,
    6. Sung TL,
    7. Chen LY.
    Extrachromosomal telomere repeat DNA is linked to ALT development via cGAS-STING DNA sensing pathway. Nat Struct Mol Biol. 2017; 24: 1124–31.
    OpenUrlCrossRefPubMed
  12. 12.↵
    2. Crasta K,
    3. Ganem NJ,
    4. Dagher R,
    5. Lantermann AB,
    6. Ivanova EV,
    7. Pan Y, et al.
    DNA breaks and chromosome pulverization from errors in mitosis. Nature. 2012; 482: 53–8.
    OpenUrlCrossRefPubMedWeb of Science
  13. 13.↵
    2. Hatch EM,
    3. Fischer AH,
    4. Deerinck TJ,
    5. Hetzer MW.
    Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell. 2013; 154: 47–60.
    OpenUrlCrossRefPubMedWeb of Science
  14. 14.↵
    2. Beck MA,
    3. Fischer H,
    4. Grabner LM,
    5. Groffics T,
    6. Winter M,
    7. Tangermann S, et al.
    DNA hypomethylation leads to cGAS-induced autoinflammation in the epidermis. EMBO J. 2021; 40: e108234.
  15. 15.↵
    2. Fuertes MB,
    3. Kacha AK,
    4. Kline J,
    5. Woo SR,
    6. Kranz DM,
    7. Murphy KM, et al.
    Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells. J Exp Med. 2011; 208: 2005–16.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    2. Samson N,
    3. Ablasser A.
    The cGAS-STING pathway and cancer. Nat Cancer. 2022; 3: 1452–63.
    OpenUrlPubMed
  17. 17.↵
    2. Ahn J,
    3. Xia T,
    4. Konno H,
    5. Konno K,
    6. Ruiz P,
    7. Barber GN.
    Inflammation-driven carcinogenesis is mediated through STING. Nat Commun. 2014; 5: 5166.
    OpenUrlCrossRefPubMed
  18. 18.↵
    2. Hou Y,
    3. Liang H,
    4. Rao E,
    5. Zheng W,
    6. Huang X,
    7. Deng L, et al.
    Non-canonical NF-κB antagonizes STING sensor-mediated DNA sensing in radiotherapy. Immunity. 2018; 49: 490–503.e4.
    OpenUrlPubMed
  19. 19.↵
    2. Larkin B,
    3. Ilyukha V,
    4. Sorokin M,
    5. Buzdin A,
    6. Vannier E,
    7. Poltorak A.
    Cutting edge: activation of STING in T cells induces type I IFN responses and cell death. J Immunol. 2017; 199: 397–402.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    2. Wu J,
    3. Dobbs N,
    4. Yang K,
    5. Yan N.
    Interferon-independent activities of mammalian STING mediate antiviral response and tumor immune evasion. Immunity. 2020; 53: 115–26.e5.
    OpenUrlCrossRefPubMed
  21. 21.↵
    2. Chan CY,
    3. Chiu DK,
    4. Yuen VW,
    5. Law CT,
    6. Wong BP,
    7. Thu KL, et al.
    CFI-402257, a TTK inhibitor, effectively suppresses hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2022; 119: e2119514119.
  22. 22.↵
    2. Chan CY,
    3. Yuen VW,
    4. Chiu DK,
    5. Goh CC,
    6. Thu KL,
    7. Cescon DW, et al.
    Polo-like kinase 4 inhibitor CFI-400945 suppresses liver cancer through cell cycle perturbation and eliciting antitumor immunity. Hepatology. 2023; 77: 729–44.
    OpenUrlPubMed
  23. 23.↵
    2. Chan FF,
    3. Yuen VW,
    4. Shen J,
    5. Chin DW,
    6. Law CT,
    7. Wong BP, et al.
    Inhibition of CAF-1 histone chaperone complex triggers cytosolic DNA and dsRNA sensing pathways and induces intrinsic immunity of hepatocellular carcinoma. Hepatology. 2024; 80: 295–311.
    OpenUrlPubMed
  24. 24.↵
    2. Luo X,
    3. Li H,
    4. Ma L,
    5. Zhou J,
    6. Guo X,
    7. Woo SL, et al.
    Expression of STING is increased in liver tissues from patients with NAFLD and promotes macrophage-mediated hepatic inflammation and fibrosis in mice. Gastroenterology. 2018; 155: 1971–84.e4.
    OpenUrlCrossRefPubMed
  25. 25.↵
    2. Nishimura S,
    3. Linares JF,
    4. L’Hermitte A,
    5. Duran A,
    6. Cid-Diaz T,
    7. Martinez-Ordonez A, et al.
    Opposing regulation of the STING pathway in hepatic stellate cells by NBR1 and p62 determines the progression of hepatocellular carcinoma. Mol Cell. 2024; 84: 4660–76.e10.
    OpenUrlPubMed
  26. 26.↵
    2. Wong PY,
    3. Chan CYK,
    4. Xue HDG,
    5. Goh CC,
    6. Cheu JWS,
    7. Tse APW, et al.
    Cell cycle inhibitors activate the hypoxia-induced DDX41/STING pathway to mediate antitumor immune response in liver cancer. JCI Insight. 2024; 9: e170532.
  27. 27.↵
    2. Pan BS,
    3. Perera SA,
    4. Piesvaux JA,
    5. Presland JP,
    6. Schroeder GK,
    7. Cumming JN, et al.
    An orally available non-nucleotide STING agonist with antitumor activity. Science. 2020; 369: eaba6098.
  28. 28.↵
    2. Wang B,
    3. Yu W,
    4. Jiang H,
    5. Meng X,
    6. Tang D,
    7. Liu D.
    Clinical applications of STING agonists in cancer immunotherapy: current progress and future prospects. Front Immunol. 2024; 15: 1485546.
  29. 29.↵
    2. Yang H,
    3. Li R,
    4. Jin S,
    5. Tian Y,
    6. Wang C,
    7. Sun Y, et al.
    Targeted nanosensitizer-augmented sono-immunotherapy with STING agonist to remodel the immune microenvironment in hepatocellular carcinoma. Acta Biomater. 2025; 199: 387–97.
    OpenUrlPubMed
  30. 30.↵
    2. Zhou ML,
    3. Liang S,
    4. Wang J,
    5. Hai LN,
    6. Peng YX,
    7. Xiong QQ, et al.
    A rationally designed cyclic dinucleotide amplifier potentiating STING activation for cancer immunotherapy. Adv Funct Mater. 2025; 35: 2414918.
Back to top

In this issue

Print
Download PDF
Email Article
Citation Tools

Jump to section