Lin TY, Lee TL, Hsu YB, Tai SK, Wang LW, Yang MH, et al. Survival analyses of different treatment modalities and clinical stage for hypopharyngeal carcinoma. Front Oncol. 2023;13:1109417. https://doi.org/10.3389/fonc.2023.1109417.
Google Scholar
Garneau JC, Bakst RL, Miles BA. Hypopharyngeal cancer: A state of the art review. Oral Oncol. 2018;86:244–50. https://doi.org/10.1016/j.oraloncology.2018.09.025.
Google Scholar
Chang CF, Wang LW, Yang MH, Chu PY. Induction chemotherapy followed by transoral laser microsurgery with or without adjuvant therapy for advanced hypopharyngeal cancer patients: A preliminary result. J Chin Med Assoc. 2024;87:803–8. https://doi.org/10.1097/JCMA.0000000000001121.
Google Scholar
Karabajakian A, Gau M, Reverdy T, Neidhardt EM, Fayette J. Induction chemotherapy in head and neck squamous cell carcinoma: a question of belief. Cancers, 2018:11. https://doi.org/10.3390/cancers11010015.
Yu W, Chen Y, Putluri N, Coarfa C, Robertson MJ, Putluri V et al. Acquisition of Cisplatin Resistance Shifts Head and Neck Squamous Cell Carcinoma Metabolism toward Neutralization of Oxidative Stress. Cancers, 2020:12. https://doi.org/10.3390/cancers12061670.
Wu P, Wu H, Tang Y, Luo S, Fang X, Xie C, et al. Whole-exome sequencing reveals novel mutations and epigenetic regulation in hypopharyngeal carcinoma. Oncotarget. 2017;8:85326–40. https://doi.org/10.18632/oncotarget.19674.
Google Scholar
Yao J, Ding Y, Liu X, Huang J, Zhang M, Zhang Y, et al. Application value of whole exome sequencing in screening and identifying novel mutations of hypopharyngeal cancer. Sci Rep. 2023;13:107. https://doi.org/10.1038/s41598-022-27273-w.
Google Scholar
Pogrebniak KL, Curtis C. Harnessing tumor evolution to circumvent resistance. Trends Genet. 2018;34:639–51. https://doi.org/10.1016/j.tig.2018.05.007.
Google Scholar
Wang S, Böhnert V, Joseph AJ, Sudaryo V, Skariah G, Swinderman JT, et al. ENPP1 is an innate immune checkpoint of the anticancer cGAMP-STING pathway in breast cancer. Proc Natl Acad Sci USA. 2023;120:e2313693120. https://doi.org/10.1073/pnas.2313693120.
Google Scholar
Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013;7:Unit7.20 https://doi.org/10.1002/0471142905.hg0720s76.
Google Scholar
Xu X, Wang Y, Bai Y, Lu J, Guo Y, Wang X, et al. Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma. Front Immunol. 2022;13:1001173 https://doi.org/10.3389/fimmu.2022.1001173.
Google Scholar
Huang Q, Hsueh CY, Shen YJ, Guo Y, Huang JM, Zhang YF, et al. Small extracellular vesicle-packaged TGFβ1 promotes the reprogramming of normal fibroblasts into cancer-associated fibroblasts by regulating fibronectin in head and neck squamous cell carcinoma. Cancer Lett. 2021;517:1–13. https://doi.org/10.1016/j.canlet.2021.05.017.
Google Scholar
Wang HC, Moi SH, Chan LP, Wu CC, Du JS, Liu PL, et al. The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy. Exp Mol Med. 2023;55:926–38. https://doi.org/10.1038/s12276-023-00984-4.
Google Scholar
Eder T, Hess AK, Konschak R, Stromberger C, Jöhrens K, Fleischer V, et al. Interference of tumour mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group. Eur J Cancer. 2019;116:67–76. https://doi.org/10.1016/j.ejca.2019.04.015.
Google Scholar
Chandrasekhar C, Kumar PS, Sarma PVGK. Novel mutations in the kinase domain of BCR-ABL gene causing imatinib resistance in chronic myeloid leukemia patients. Sci Rep. 2019;9:2412. https://doi.org/10.1038/s41598-019-38672-x.
Google Scholar
Kato K, Nishimasu H, Okudaira S, Mihara E, Ishitani R, Takagi J, et al. Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin signaling. Proc Natl Acad Sci USA. 2012;109:16876–81. https://doi.org/10.1073/pnas.1208017109.
Google Scholar
An Y, Zhu J, Xie Q, Feng J, Gong Y, Fan Q, et al. Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling. Adv Sci. 2024;11:2308131 https://doi.org/10.1002/advs.202308131.
Google Scholar
Newman JR, Connolly TM, Illing EA, Kilgore ML, Locher JL, Carroll WR. Survival trends in hypopharyngeal cancer: a population-based review. Laryngoscope. 2015;125:624–9. https://doi.org/10.1002/lary.24915.
Google Scholar
Haddad RI, Posner M, Hitt R, Cohen EEW, Schulten J, Lefebvre JL, et al. Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions. Ann Oncol. 2018;29:1130–40. https://doi.org/10.1093/annonc/mdy102.
Google Scholar
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357:1695–704. https://doi.org/10.1056/NEJMoa071028.
Google Scholar
Gauss C, Stone LD, Ghafouri M, Quan D, Johnson J, Fribley AM et al. Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas. Cells, 2024, 13. https://doi.org/10.3390/cells13121018.
Kanno Y, Chen CY, Lee HL, Chiou JF, Chen YJ. Molecular mechanisms of chemotherapy resistance in head and neck cancers. Front Oncol. 2021;11:640392. https://doi.org/10.3389/fonc.2021.640392.
Google Scholar
Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333:1154–7. https://doi.org/10.1126/science.1206923.
Google Scholar
Ruiz-Fernández De Córdoba, Moreno B, Valencia H, Perurena K, Ruedas P N, Walle T, et al. Tumor ENPP1 (CD203a)/Haptoglobin axis exploits myeloid-derived suppressor cells to promote post-radiotherapy local recurrence in breast cancer. Cancer Discov. 2022;12:1356–77. https://doi.org/10.1158/2159-8290.CD-21-0932.
Google Scholar
Attalla SS, Boucher J, Proud H, Taifour T, Zuo D, Sanguin-Gendreau V, et al. HER2Δ16 engages ENPP1 to promote an immune-cold microenvironment in breast cancer. Cancer Immunol Res. 2023;11:1184–202. https://doi.org/10.1158/2326-6066.CIR-22-0140.
Google Scholar
Santos L, Tomatis F, Ferreira HRS, Almeida SFF, Ciputra E, Sereno J, et al. ENPP1 induces blood-brain barrier dysfunction and promotes brain metastasis formation in HER2-positive breast cancer. Neuro-Oncol. 2024;27:167–83.
Google Scholar
Ma C, Zhao J, Zhou L, Jia C, Shi Y, Li X, et al. Targeting ENPP1 depletion may be a promising therapeutic strategy for treating oral squamous cell carcinoma via cytotoxic autophagy-related apoptosis. FASEB J. 2024;38:e23420. https://doi.org/10.1096/fj.202301835R.
Google Scholar
Wang H, Ye F, Zhou C, Cheng Q, Chen H. High expression of ENPP1 in high-grade serous ovarian carcinoma predicts poor prognosis and as a molecular therapy target. PLoS ONE. 2021;16:e0245733. https://doi.org/10.1371/journal.pone.0245733.
Google Scholar
Hu M, Guo W, Liao Y, Xu D, Sun B, Song H, et al. Dysregulated ENPP1 increases the malignancy of human lung cancer by inducing epithelial-mesenchymal transition phenotypes and stem cell features. Am J Cancer Res. 2019;9:134–44.
Google Scholar
Carozza JA, Cordova AF, Brown JA, AlSaif Y, Böhnert V, Cao X, et al. ENPP1’s regulation of extracellular cGAMP is a ubiquitous mechanism of attenuating STING signaling. Proc Natl Acad Sci USA. 2022;119:e2119189119. https://doi.org/10.1073/pnas.2119189119.
Google Scholar
Li J, Duran MA, Dhanota N, Chatila WK, Bettigole SE, Kwon J, et al. Metastasis and immune evasion from extracellular cGAMP hydrolysis. Cancer Discov. 2021;11:1212–27. https://doi.org/10.1158/2159-8290.CD-20-0387.
Google Scholar
Ritchie C, Carozza JA, Li L. Biochemistry, cell biology, and pathophysiology of the innate immune cGAS–cGAMP–STING pathway. Annu Rev Biochem. 2022;91:599–628. https://doi.org/10.1146/annurev-biochem-040320-101629.
Google Scholar
de Oliveira Mann CC, Orzalli MH, King DS, Kagan JC, Lee ASY, Kranzusch PJ. Modular architecture of the STING C-terminal tail allows interferon and NF-κB signaling adaptation. Cell Rep. 2019;27:1165–75.e5. https://doi.org/10.1016/j.celrep.2019.03.098.
Google Scholar
Wu J, Dobbs N, Yang K, Yan N. Interferon-independent activities of mammalian STING mediate antiviral response and tumor immune evasion. Immunity. 2020;53:115–26.e5. https://doi.org/10.1016/j.immuni.2020.06.009.
Google Scholar
Zhang ZD, Lin YL, Zhang HY, Zuo C, Zhu ZL, Wang XY, et al. MITA/STING-driven CD38 induction in Siglec-Flow macrophages promotes regulatory T cell survival and non-small cell lung cancer progression. Dev Cell. 2026;61:638–54.e8. https://doi.org/10.1016/j.devcel.2025.12.007.
Google Scholar
Song H, Chen L, Pan X, Shen Y, Ye M, Wang G, et al. Targeting tumor monocyte-intrinsic PD-L1 by rewiring STING signaling and enhancing STING agonist therapy. Cancer Cell. 2025;43:503–18.e10. https://doi.org/10.1016/j.ccell.2025.02.014.
Google Scholar
Hong C, Schubert M, Tijhuis AE, Requesens M, Roorda M, Van Den Brink A, et al. cGAS–STING drives the IL-6-dependent survival of chromosomally instable cancers. Nature. 2022;607:366–73. https://doi.org/10.1038/s41586-022-04847-2.
Google Scholar
Vasiyani H, Mane M, Rana K, Shinde A, Roy M, Singh J, et al. DNA damage induces STING-mediated IL-6-STAT3 survival pathway in triple-negative breast cancer cells and decreased survival of breast cancer patients. Apoptosis. 2022;27:961–78. https://doi.org/10.1007/s10495-022-01763-8.
Google Scholar
Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481:287–94. https://doi.org/10.1038/nature10760.
Google Scholar
Osman AA, Arslan E, Bartels M, Michikawa C, Lindemann A, Tomczak K, et al. Dysregulation and epigenetic reprogramming of NRF2 signaling axis promote acquisition of Cisplatin resistance and metastasis in head and neck squamous cell carcinoma. Clin Cancer Res. 2023;29:1344–59. https://doi.org/10.1158/1078-0432.CCR-22-2747.
Google Scholar
de Bakker T, Maes A, Dragan T, Martinive P, Penninckx S, Van Gestel D. Strategies to overcome intrinsic and acquired resistance to chemoradiotherapy in head and neck cancer. Cells, 2024:14. https://doi.org/10.3390/cells14010018.
Becker AS, Klauk F, Freitag T, Strüder DF, Schneider B, Zimpfer A, et al. Inhibition of platin-induced BCL2 increase overcomes chemoresistance in squamous cell carcinoma of the head and neck through resensitization to cell death. Transl Oncol. 2025;53:102308. https://doi.org/10.1016/j.tranon.2025.102308.
Google Scholar
Jeong E, Kim HL, Park S, Jang S, Ku J, Kim H, et al. HERC1 oncogene enhances stemness and tumorigenic potential in CD44(+)-derived organoids of head and neck squamous cell carcinoma through IL-6/STAT3 signaling. Oncogene. 2026;45:1840–55. https://doi.org/10.1038/s41388-026-03725-9.
Google Scholar
Nazari F, Oklejas AE, Nör JE, Pearson AT, Jackson TL. In silico models accurately predict in vivo response for IL6 blockade in head and neck cancer. Cancer Res. 2020;80:1451–60. https://doi.org/10.1158/0008-5472.CAN-19-1846.
Google Scholar
Gajewski TF, Higgs EF. Immunotherapy with a sting. Science. 2020;369:921–2. https://doi.org/10.1126/science.abc6622.
Google Scholar
