In Vitro Models of Head and Neck Cancer: Comparison
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Please note this is a comparison between Version 2 by Enar Jumaniyazova and Version 4 by Jason Zhu.

For several decades now, researchers have been trying to answer the demand of clinical oncologists to create an ideal preclinical model of head and neck squamous cell carcinoma (HNSCC) that is accessible, reproducible, and relevant. Over the past years, the development of cellular technologies has naturally allowed peopleus to move from primitive short-lived primary 2D cell cultures to complex patient-derived 3D models that reproduce the cellular composition, architecture, mutational, or viral load of native tumor tissue. Depending on the tasks and capabilities, a scientific laboratory can choose from several types of models: primary cell cultures, immortalized cell lines, spheroids or heterospheroids, tissue engineering models, bioprinted models, organoids, tumor explants, and histocultures. HNSCC in vitro models make it possible to screen agents with potential antitumor activity, study the contribution of the tumor microenvironment to its progression and metastasis, determine the prognostic significance of individual biomarkers (including using genetic engineering methods), study the effect of viral infection on the pathogenesis of the disease, and adjust treatment tactics for a specific patient or groups of patients. Promising experimental results have created a scientific basis for the registration of several clinical studies using HNSCC in vitro models.

  • head and neck squamous cell carcinoma
  • in vitro models
  • 3D models
  • viral infection
  • personalized medicine
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References

  1. Barsouk, A.; Aluru, J.S.; Rawla, P.; Saginala, K.; Barsouk, A. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med. Sci. 2023, 11, 42. 1. Barsouk, A.; Aluru, J.S.; Rawla, P.; Saginala, K.; Barsouk, A. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med. Sci. 2023, 11, 42. https://doi.org/10.3390/medsci11020042.2. Johnson, D.E.; Burtness, B.; Leemans, C.R.; Lui, V.W.Y.; Bauman, J.E.; Grandis, J.R. Head and neck squamous cell car-cinoma. Nat. Rev. Dis. Primers 2020, 6, 92. https://doi.org/10.1038/s41572-020-00224-3.3. Nissi, L.; Suilamo, S.; Kytö, E.; Vaittinen, S.; Irjala, H.; Minn, H. Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume. Clin. Transl. Radiat. Oncol. 2021, 27, 139–146. https://doi.org/10.1016/j.ctro.2021.01.013.4. Boguszewicz, Ł. Predictive Biomarkers for Response and Toxicity of Induction Chemotherapy in Head and Neck Cancers. Front. Oncol. 2022, 12, 900903. https://doi.org/10.3389/fonc.2022.900903.5. Schanne, D.H.; Koch, A.; Elicin, O.; Giger, R.; Medová, M.; Zimmer, Y.; Aebersold, D.M. Prognostic and Predictive Biomarkers in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy—A Systematic Review. Biomedicines 2022, 10, 3288. https://doi.org/10.3390/biomedicines10123288.6. Budach, V.; Tinhofer, I. Novel prognostic clinical factors and biomarkers for outcome prediction in head and neck cancer: A systematic review. Lancet Oncol. 2019, 20, e313–e326. https://doi.org/10.1016/s1470-2045(19)30177-9.7. Chaves, P.; Garrido, M.; Oliver, J.; Pérez-Ruiz, E.; Barragan, I.; Rueda-Domínguez, A. Preclinical models in head and neck squamous cell carcinoma. Br. J. Cancer 2023, 128, 1819–1827. https://doi.org/10.1038/s41416-023-02186-1.8. Seliger, B.; Al-Samadi, A.; Yang, B.; Salo, T.; Wickenhauser, C. In vitro models as tools for screening treatment options of head and neck cancer. Front. Med. 2022, 9, 971726. https://doi.org/10.3389/fmed.2022.971726.9. Easty, D.M.; Easty, G.C.; Carter, R.L.; Monaghan, P.; Butler, L.J. Ten human carcinoma cell lines derived from squamous carcinomas of the head and neck. Br. J. Cancer 1981, 43, 772–785. https://doi.org/10.1038/bjc.1981.115.10. Lepikhova, T.; Karhemo, P.-R.; Louhimo, R.; Yadav, B.; Murumägi, A.; Kulesskiy, E.; Kivento, M.; Sihto, H.; Grénman, R.; Syrjänen, S.M.; et al. Drug-sensitivity screening and genomic characterization of 45 hpV-negative head and neck car-cinoma cell lines for novel biomarkers of drug efficacy. Mol. Cancer Ther. 2018, 17, 2060–2071. https://doi.org/10.1158/1535-7163.mct-17-0733.11. Greaney-Davies, F.S.; Risk, J.M.; Robinson, M.; Liloglou, T.; Shaw, R.J.; Schache, A.G. Essential characterisation of human papillomavirus positive head and neck cancer cell lines. Oral Oncol. 2020, 103, 104613. https://doi.org/10.1016/j.oraloncology.2020.104613.12. Lin, C.J.; Grandis, J.R.; Carey, T.E.; Gollin, S.M.; Whiteside, T.L.; Koch, W.M.; Ferris, R.L.; Lai, S.Y. Head and neck squamous cell carcinoma cell lines: Established models and rationale for selection. Head Neck 2007, 29, 163–188. https://doi.org/10.1002/hed.20478.13. Close, D.A.; Wang, A.X.; Kochanek, S.J.; Shun, T.; Eiseman, J.L.; Johnston, P.A. Implementation of the NCI-60 Human Tumor Cell Line Panel to Screen 2260 Cancer Drug Combinations to Generate >3 Million Data Points Used to Populate a Large Matrix of Anti-Neoplastic Agent Combinations (ALMANAC) Database. SLAS Discov. Adv. Sci. Drug Discov. 2019, 24, 242–263. https://doi.org/10.1177/2472555218812429.14. American Type Culture Collection. Head and Neck Cancer Panel TCP-1012TM. In Medical Radiology; Springer: Cham, Switzerland, 2022; pp. 137–157. https://doi.org/10.1007/174_2017_47.15. Zhao, M.; Sano, D.; Pickering, C.R.; Jasser, S.A.; Henderson, Y.C.; Clayman, G.L.; Sturgis, E.M.; Ow, T.J.; Lotan, R.; Carey, T.; et al. Assembly and initial characterization of a panel of 85 genomically validated cell lines from diverse head and neck tumor sites. Clin. Cancer Res. 2011, 17, 7248–7264. https://doi.org/10.1158/1078-0432.ccr-11-0690.16. Li, H.; Wawrose, J.S.; Gooding, W.E.; Garraway, L.A.; Lui, V.W.Y.; Peyser, N.D.; Grandis, J.R. Genomic analysis of head and neck squamous cell carcinoma cell lines and human tumors: A rational approach to preclinical model selection. Mol. Cancer Res. 2014, 12, 571–582. https://doi.org/10.1158/1541-7786.mcr-13-0396.17. Kapałczyńska, M.; Kolenda, T.; Przybyła, W.; Zajączkowska, M.; Teresiak, A.; Filas, V.; Ibbs, M.; Bliźniak, R.; Łuczewski, L.; Lamperska, K. 2D and 3D cell cultures—A comparison of different types of cancer cell cultures. Arch. Med. Sci. 2018, 14, 910–919. https://doi.org/10.5114/aoms.2016.63743.18. Jubelin, C.; Muñoz-Garcia, J.; Griscom, L.; Cochonneau, D.; Ollivier, E.; Heymann, M.-F.; Vallette, F.M.; Oliver, L.; Heymann, D. Three-dimensional in vitro culture models in oncology research. Cell Biosci. 2022, 12, 155. https://doi.org/10.1186/s13578-022-00887-3.19. Park, S.-B.; Jung, W.K.; Kim, H.R.; Yu, H.-Y.; Kim, Y.H.; Kim, J. Esculetin has therapeutic potential via the proapoptotic signaling pathway in A253 human submandibular salivary gland tumor cells. Exp. Ther. Med. 2022, 24, 533. https://doi.org/10.3892/etm.2022.11460.20. Colley, H.E.; Hearnden, V.; Jones, A.V.; Weinreb, P.H.; Violette, S.M.; MacNeil, S.; Thornhill, M.H.; Murdoch, C. De-velopment of tissue-engineered models of oral dysplasia and early invasive oral squamous cell carcinoma. Br. J. Cancer 2011, 105, 1582–1592. https://doi.org/10.1038/bjc.2011.403.21. Bernhard, W.; Barreto, K.; El-Sayed, A.; DeCoteau, J.; Geyer, C.R. Imaging Immune Cells Using Fc Domain Probes in Mouse Cancer Xenograft Models. Cancers 2022, 14, 300. https://doi.org/10.3390/cancers14020300.22. Bernareggi, D.; Xie, Q.; Prager, B.C.; Yun, J.; Cruz, L.S.; Pham, T.V.; Kim, W.; Lee, X.; Coffey, M.; Zalfa, C.; et al. CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity. Nat. Commun. 2022, 13, 1899. https://doi.org/10.1038/s41467-022-29469-0.23. Hsu, C.-M.; Yang, M.-Y.; Tsai, M.-S.; Chang, G.-H.; Yang, Y.-H.; Tsai, Y.-T.; Wu, C.-Y.; Chang, S.-F. Dihydroisotanshinone i as a treatment option for head and neck squamous cell carcinomas. Int. J. Mol. Sci. 2021, 22, 8881. https://doi.org/10.3390/ijms22168881.24. Cekanova, M.; Rathore, K. Animal models and therapeutic molecular targets of cancer: Utility and limitations. Drug Des. Dev. Ther. 2014, 8, 1911–1922. https://doi.org/10.2147/dddt.s49584.25. Moya-Garcia, C.R.; Okuyama, H.; Sadeghi, N.; Li, J.; Tabrizian, M.; Li-Jessen, N.Y.K. In vitro models for head and neck cancer: Current status and future perspective. Front. Oncol. 2022, 12, 960340. https://doi.org/10.3389/fonc.2022.960340.26. Morrissey, B.; Blyth, K.; Carter, P.; Chelala, C.; Jones, L.; Holen, I.; Speirs, V. The Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) Framework: Encouraging Reduction, Replacement, and Refinement in Animal Re-search. PLoS Biol. 2017, 15, e2000719. https://doi.org/10.1371/journal.pbio.2000719.27. Tenschert, E.; Kern, J.; Affolter, A.; Rotter, N.; Lammert, A. Optimisation of Conditions for the Formation of Spheroids of Head and Neck Squamous Cell Carcinoma Cell Lines for Use as Animal Alternatives. Altern. Lab. Anim. 2022, 50, 414–422. https://doi.org/10.1177/02611929221135042.28. Kimlin, L.C.; Casagrande, G.; Virador, V.M. In vitro three-dimensional (3D) models in cancer research: An update. Mol. Carcinog. 2013, 52, 167–182. https://doi.org/10.1002/mc.21844.29. Han, S.J.; Kwon, S.; Kim, K.S. Challenges of applying multicellular tumor spheroids in preclinical phase. Cancer Cell Int. 2021, 21, 152. https://doi.org/10.1186/s12935-021-01853-8.30. Costa, E.C.; Moreira, A.F.; De Melo-Diogo, D.; Gaspar, V.M.; Carvalho, M.P.; Correia, I.J. 3D tumor spheroids: An overview on the tools and techniques used for their analysis. Biotechnol. Adv. 2016, 34, 1427–1441. https://doi.org/10.1016/j.biotechadv.2016.11.002.31. Thakuri, P.S.; Gupta, M.; Plaster, M.; Tavana, H. Quantitative Size-Based Analysis of Tumor Spheroids and Responses to Therapeutics. ASSAY Drug Dev. Technol. 2019, 17, 140–149. https://doi.org/10.1089/adt.2018.895.32. Cui, X.; Hartanto, Y.; Zhang, H. Advances in multicellular spheroids formation. J. R. Soc. Interface 2017, 14, 20160877. https://doi.org/10.1098/rsif.2016.0877.33. Lin, R.; Chang, H. Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol. J. 2008, 3, 1172–1184. https://doi.org/10.1002/biot.200700228.34. Raghavan, S.; Mehta, P.; Horst, E.N.; Ward, M.R.; Rowley, K.R.; Mehta, G. Comparative analysis of tumor spheroid generation techniques for differentialin vitrodrug toxicity. Oncotarget 2016, 7, 16948–16961. https://doi.org/10.18632/oncotarget.7659.35. Luoto, K.R.; Kumareswaran, R.; Bristow, R.G. Tumor hypoxia as a driving force in genetic instability. Genome Integr. 2013, 4, 5–5. https://doi.org/10.1186/2041-9414-4-5.36. Yasui, H.; Kawai, T.; Matsumoto, S.; Saito, K.; Devasahayam, N.; Mitchell, J.B.; Camphausen, K.; Inanami, O.; Krishna, M.C. Quantitative imaging of pO2 in orthotopic murine gliomas: Hypoxia correlates with resistance to radiation. Free. Radic. Res. 2017, 51, 861–871. https://doi.org/10.1080/10715762.2017.1388506.37. Gatenby, R.A.; Gillies, R.J. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 2004, 4, 891–899. https://doi.org/10.1038/nrc1478.38. Mehta, G.; Hsiao, A.Y.; Ingram, M.; Luker, G.D.; Takayama, S. Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J. Control. Release 2012, 164, 192–204. https://doi.org/10.1016/j.jconrel.2012.04.045.39. Ham, S.L.; Joshi, R.; Thakuri, P.S.; Tavana, H. Liquid-based three-dimensional tumor models for cancer research and drug discovery. Exp. Biol. Med. 2016, 241, 939–954. https://doi.org/10.1177/1535370216643772.40. Santi, M.; Mapanao, A.K.; Cappello, V.; Voliani, V. Production of 3D tumor models of head and neck squamous cell carcinomas for nanotheranostics assessment. ACS Biomater. Sci. Eng. 2020, 6, 4862–4869. https://doi.org/10.1021/acsbiomaterials.0c00617.41. Tevis, K.M.; Colson, Y.L.; Grinstaff, M.W. Embedded Spheroids as Models of the Cancer Microenvironment. Adv. Biosyst. 2017, 1, 1700083. https://doi.org/10.1002/adbi.201700083.42. Hagemann, J.; Jacobi, C.; Gstoettner, S.; Welz, C.; Schwenk-Zieger, S.; Stauber, R.; Strieth, S.; Kuenzel, J.; Baumeister, P.; Becker, S. Therapy testing in a spheroid-based 3D cell culture model for head and neck squamous cell carcinoma. J. Vis. Exp. 2018, 2018, e57012. https://doi.org/10.3791/57012.43. Shao, S.; Scholtz, L.U.; Gendreizig, S.; Martínez-Ruiz, L.; Florido, J.; Escames, G.; Schürmann, M.; Hain, C.; Hose, L.; Mentz, A.; et al. Primary head and neck cancer cell cultures are susceptible to proliferation of Epstein-Barr virus infected lymphocytes. BMC Cancer 2023, 23, 47. https://doi.org/10.1186/s12885-022-10481-y.44. Hagemann, J.; Jacobi, C.; Hahn, M.; Schmid, V.; Welz, C.; Schwenk-Zieger, S.; Stauber, R.; Baumeister, P.; Becker, S. Spheroid-based 3D cell cultures enable personalized therapy testing and drug discovery in head and neck cancer. An-ticancer. Res. 2017, 37, 2201–2210. https://doi.org/10.21873/anticanres.11555.45. Vakhshiteh, F.; Bagheri, Z.; Soleimani, M.; Ahvaraki, A.; Pournemat, P.; Alavi, S.E.; Madjd, Z. Heterotypic tumor spheroids: A platform for nanomedicine evaluation. J. Nanobiotechnol. 2023, 21, 249. https://doi.org/10.1186/s12951-023-02021-y.46. Yakavets, I.; Francois, A.; Lamy, L.; Piffoux, M.; Gazeau, F.; Wilhelm, C.; Zorin, V.; Silva, A.K.A.; Bezdetnaya, L. Effect of stroma on the behavior of temoporfin-loaded lipid nanovesicles inside the stroma-rich head and neck carcinoma spheroids. J. Nanobiotechnol. 2021, 19, 3. https://doi.org/10.1186/s12951-020-00743-x.47. Yakavets, I.; Jenard, S.; Francois, A.; Maklygina, Y.; Loschenov, V.; Lassalle, H.-P.; Dolivet, G.; Bezdetnaya, L. Stroma-rich co-culture multicellular tumor spheroids as a tool for photoactive drugs screening. J. Clin. Med. 2019, 8, 1686. https://doi.org/10.3390/jcm8101686.48. Dehghankelishadi, P.; Maritz, M.F.; Badiee, P.; Thierry, B. High density lipoprotein nanoparticle as delivery system for radio-sensitising miRNA: An investigation in 2D/3D head and neck cancer models. Int. J. Pharm. 2022, 617, 121585. https://doi.org/10.1016/j.ijpharm.2022.121585.49. Magan, M.; Wiechec, E.; Roberg, K. CAFs affect the proliferation and treatment response of head and neck cancer spheroids during co-culturing in a unique in vitro model. Cancer Cell Int. 2020, 20, 599. https://doi.org/10.1186/s12935-020-01718-6.50. He, Y.; Deng, P.; Yan, Y.; Zhu, L.; Chen, H.; Li, T.; Li, Y.; Li, J. Matrisome provides a supportive microenvironment for oral squamous cell carcinoma progression. J. Proteom. 2022, 253, 104454. https://doi.org/10.1016/j.jprot.2021.104454.51. Anbazhagan, R.; Sakakura, T.; Gusterson, B.A. The distribution of immuno-reactive tenascin in the epitheli-al-mesenchymal junctional areas of benign and malignant squamous epithelia. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 1990, 59, 59–63. https://doi.org/10.1007/bf02899388.52. Berndt, A.; Hyckel, P.; Kosmehl, H.; Könneker, A. Dreidimensionales In-vitro-Invasionsmodell für orale Plattenepi-thelkarzinome. Mund-Kiefer-und Gesichtschirurgie 1998, 2, 256–260. https://doi.org/10.1007/s100060050070.53. Fischbach, C.; Chen, R.; Matsumoto, T.; Schmelzle, T.; Brugge, J.S.; Polverini, P.J.; Mooney, D.J. Engineering tumors with 3D scaffolds. Nat. Methods 2007, 4, 855–860. https://doi.org/10.1038/nmeth1085.54. Rossi, L.; Corvò, R.; Videtic, G.M.; Paulus, R.; Singh, A.K.; Chang, J.Y.; Parker, W.; Olivier, K.R.; Timmerman, R.D.; Komaki, R.R.; et al. Retinoic acid modulates the radiosensitivity of head-and-neck squamous carcinoma cells grown in collagen gel. Int. J. Radiat. Oncol. 2002, 53, 1319–1327. https://doi.org/10.1016/s0360-3016(02)02865-1.55. Miserocchi, G.; Cocchi, C.; De Vita, A.; Liverani, C.; Spadazzi, C.; Calpona, S.; Di Menna, G.; Bassi, M.; Meccariello, G.; De Luca, G.; et al. Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas. Cancer Biol. Med. 2021, 18, 502–516. https://doi.org/10.20892/j.issn.2095-3941.2020.0482.56. Gu, C.; Zhang, Y.; Chen, D.; Liu, H.; Mi, K. Tunicamycin-induced endoplasmic reticulum stress inhibits chemoresistance of FaDu hypopharyngeal carcinoma cells in 3D collagen I cultures and in vivo. Exp. Cell Res. 2021, 405, 112725. https://doi.org/10.1016/j.yexcr.2021.112725.57. Young, M.; Rodenhizer, D.; Dean, T.; D’Arcangelo, E.; Xu, B.; Ailles, L.; McGuigan, A.P. A TRACER 3D Co-Culture tumour model for head and neck cancer. Biomaterials 2018, 164, 54–69. https://doi.org/10.1016/j.biomaterials.2018.01.038.58. Dean, T.; Li, N.T.; Cadavid, J.L.; Ailles, L.; McGuigan, A.P. A TRACER culture invasion assay to probe the impact of cancer associated fibroblasts on head and neck squamous cell carcinoma cell invasiveness. Biomater. Sci. 2020, 8, 3078–3094. https://doi.org/10.1039/c9bm02017a.59. Gu, Y.; Schwarz, B.; Forget, A.; Barbero, A.; Martin, I.; Shastri, V.P. Advanced bioink for 3D bioprinting of complex free-standing structures with high stiffness. Bioengineering 2020, 7, 141. https://doi.org/10.3390/bioengineering7040141.60. Zhang, Y.S.; Duchamp, M.; Oklu, R.; Ellisen, L.W.; Langer, R.; Khademhosseini, A. Bioprinting the Cancer Microenvi-ronment. ACS Biomater. Sci. Eng. 2016, 2, 1710–1721. https://doi.org/10.1021/acsbiomaterials.6b00246.61. Murphy, S.V.; Atala, A. 3D bioprinting of tissues and organs. Nat. Biotechnol. 2014, 32, 773–785. https://doi.org/10.1038/nbt.2958.62. Hoarau-Véchot, J.; Rafii, A.; Touboul, C.; Pasquier, J. Halfway between 2D and animal models: Are 3D cultures the ideal tool to study cancer-microenvironment interactions? Int. J. Mol. Sci. 2018, 19, 181. https://doi.org/10.3390/ijms19010181.63. Kort-Mascort, J.; Bao, G.; Elkashty, O.; Flores-Torres, S.; Munguia-Lopez, J.G.; Jiang, T.; Ehrlicher, A.J.; Mongeau, L.; Tran, S.D.; Kinsella, J.M. Decellularized Extracellular Matrix Composite Hydrogel Bioinks for the Development of 3D Bioprinted Head and Neck in Vitro Tumor Models. ACS Biomater. Sci. Eng. 2021, 7, 5288–5300. https://doi.org/10.1021/acsbiomaterials.1c00812.64. Kort-Mascort, J.; Shen, M.L.; Martin, E.; Flores-Torres, S.; Pardo, L.A.; Siegel, P.M.; Tran, S.D.; Kinsella, J.M. Bioprinted cancer-stromal in-vitro models in a decellularized ECM-based bioink exhibit progressive remodeling and maturation. Biomed. Mater. 2023, 18, 045022. https://doi.org/10.1088/1748-605x/acd830.65. Saglam-Metiner, P.; Gulce-Iz, S.; Biray-Avci, C. Bioengineering-inspired three-dimensional culture systems: Organoids to create tumor microenvironment. Gene 2019, 686, 203–212. https://doi.org/10.1016/j.gene.2018.11.058.66. Barbet, V.; Broutier, L. Future Match Making: When Pediatric Oncology Meets Organoid Technology. Front. Cell Dev. Biol. 2021, 9, 674219. https://doi.org/10.3389/fcell.2021.674219.67. Kim, S.; Choung, S.; Sun, R.X.; Ung, N.; Hashemi, N.; Fong, E.J.; Lau, R.; Spiller, E.; Gasho, J.; Foo, J.; et al. Comparison of Cell and Organoid-Level Analysis of Patient-Derived 3D Organoids to Evaluate Tumor Cell Growth Dynamics and Drug Response. SLAS Discov. Adv. Sci. Drug Discov. 2020, 25, 744–754. https://doi.org/10.1177/2472555220915827.68. Clevers, H. Modeling Development and Disease with Organoids. Cell 2016, 165, 1586–1597. https://doi.org/10.1016/j.cell.2016.05.082.69. Papaccio, F.; Cabeza-Segura, M.; Garcia-Micò, B.; Tarazona, N.; Roda, D.; Castillo, J.; Cervantes, A. Will Organoids Fill the Gap towards Functional Precision Medicine? J. Pers. Med. 2022, 12, 1939. https://doi.org/10.3390/jpm12111939.70. Yan, H.H.N.; Siu, H.C.; Law, S.; Ho, S.L.; Yue, S.S.K.; Tsui, W.Y.; Chan, D.; Chan, A.S.; Ma, S.; Lam, K.O.; et al. A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Ther-apeutic Screening. Cell Stem Cell 2018, 23, 882–897.e811. https://doi.org/10.1016/j.stem.2018.09.016.71. Driehuis, E.; Kretzschmar, K.; Clevers, H. Establishment of patient-derived cancer organoids for drug-screening appli-cations. Nat. Protoc. 2020, 15, 3380–3409. https://doi.org/10.1038/s41596-020-0379-4.72. Hughes, C.S.; Postovit, L.M.; Lajoie, G.A. Matrigel: A complex protein mixture required for optimal growth of cell culture. Proteomics 2010, 10, 1886–1890. https://doi.org/10.1002/pmic.200900758.73. Kaur, S.; Kaur, I.; Rawal, P.; Tripathi, D.M.; Vasudevan, A. Non-matrigel scaffolds for organoid cultures. Cancer Lett. 2021, 504, 58–66. https://doi.org/10.1016/j.canlet.2021.01.025.74. Kozlowski, M.T.; Crook, C.J.; Ku, H.T. Towards organoid culture without Matrigel. Commun. Biol. 2021, 4, 1387. https://doi.org/10.1038/s42003-021-02910-8.75. Tanaka, N.; Osman, A.A.; Takahashi, Y.; Lindemann, A.; Patel, A.A.; Zhao, M.; Takahashi, H.; Myers, J.N. Head and neck cancer organoids established by modification of the CTOS method can be used to predict in vivo drug sensitivity. Oral Oncol. 2018, 87, 49–57. https://doi.org/10.1016/j.oraloncology.2018.10.018.76. Kijima, T.; Nakagawa, H.; Shimonosono, M.; Chandramouleeswaran, P.M.; Hara, T.; Sahu, V.; Kasagi, Y.; Kikuchi, O.; Tanaka, K.; Giroux, V.; et al. Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells. Cell. Mol. Gastroenterol. Hepatol. 2019, 7, 73–91. https://doi.org/10.1016/j.jcmgh.2018.09.003.77. Zhao, H.; Hu, C.-Y.; Chen, W.-M.; Huang, P. Lactate Promotes Cancer Stem-like Property of Oral Sequamous Cell Car-cinoma. Curr. Med. Sci. 2019, 39, 403–409. https://doi.org/10.1007/s11596-019-2050-2.78. Perréard, M.; Florent, R.; Divoux, J.; Grellard, J.-M.; Lequesne, J.; Briand, M.; Clarisse, B.; Rousseau, N.; Lebreton, E.; Dubois, B.; et al. ORGAVADS: Establishment of tumor organoids from head and neck squamous cell carcinoma to assess their response to innovative therapies. BMC Cancer 2023, 23, 223. https://doi.org/10.1186/s12885-023-10692-x.79. Wang, X.-W.; Xia, T.-L.; Tang, H.-C.; Liu, X.; Han, R.; Zou, X.; Zhao, Y.-T.; Chen, M.-Y.; Li, G. Establishment of a pa-tient-derived organoid model and living biobank for nasopharyngeal carcinoma. Ann. Transl. Med. 2022, 10, 526–526. https://doi.org/10.21037/atm-22-1076.80. Tuveson, D.A.; Clevers, H. Cancer modeling meets human organoid technology. Science 2019, 364, 952–955. https://doi.org/10.1126/science.aaw6985.81. Driehuis, E.; Kolders, S.; Spelier, S.; Lõhmussaar, K.; Willems, S.M.; Devriese, L.A.; de Bree, R.; de Ruiter, E.J.; Korving, J.; Begthel, H.; et al. Oral mucosal organoids as a potential platform for personalized cancer therapy. Cancer Discov. 2019, 9, 852–871. https://doi.org/10.1158/2159-8290.cd-18-1522.82. Wu, K.Z.; Adine, C.; Mitriashkin, A.; Aw, B.J.J.; Iyer, N.G.; Fong, E.L.S. Making In Vitro Tumor Models Whole Again. Adv. Healthc. Mater. 2023, 12, e2202279. https://doi.org/10.1002/adhm.202202279.83. Engelmann, L.; Thierauf, J.; Laureano, N.K.; Stark, H.-J.; Prigge, E.-S.; Horn, D.; Freier, K.; Grabe, N.; Rong, C.; Federspil, P.; et al. Organotypic co-cultures as a novel 3d model for head and neck squamous cell carcinoma. Cancers 2020, 12, 2330. https://doi.org/10.3390/cancers12082330.84. Dohmen, A.J.; Sanders, J.; Canisius, S.; Jordanova, E.S.; Aalbersberg, E.A.; Brekel, M.W.v.D.; Neefjes, J.; Zuur, C.L. Sponge-supported cultures of primary head and neck tumors for an optimized preclinical model. Oncotarget 2018, 9, 25034–25047. https://doi.org/10.18632/oncotarget.25244.85. Lee, J.; You, J.H.; Shin, D.; Roh, J.-L. Ex vivo culture of head and neck cancer explants in cell sheet for testing chemo-therapeutic sensitivity. J. Cancer Res. Clin. Oncol. 2020, 146, 2497–2507. https://doi.org/10.1007/s00432-020-03306-7.86. Demers, I.; Donkers, J.; Kremer, B.; Speel, E.J. Ex Vivo Culture Models to Indicate Therapy Response in Head and Neck Squamous Cell Carcinoma. Cells 2020, 9, 2527. https://doi.org/10.3390/cells9112527.87. Peria, M.; Donnadieu, J.; Racz, C.; Ikoli, J.; Galmiche, A.; Chauffert, B.; Page, C. Evaluation of individual sensitivity of head and neck squamous cell carcinoma to cetuximab by short-term culture of tumor slices. Head Neck 2016, 38, E911–E915. https://doi.org/10.1002/hed.24126.88. Gerlach, M.M.; Merz, F.; Wichmann, G.; Kubick, C.; Wittekind, C.; Lordick, F.; Dietz, A.; Bechmann, I. Slice cultures from head and neck squamous cell carcinoma: A novel test system for drug susceptibility and mechanisms of resistance. Br. J. Cancer 2014, 110, 479–488. https://doi.org/10.1038/bjc.2013.700.89. Tevlek, A.; Kecili, S.; Ozcelik, O.S.; Kulah, H.; Tekin, H.C. Spheroid Engineering in Microfluidic Devices. ACS Omega 2023, 8, 3630–3649. https://doi.org/10.1021/acsomega.2c06052.90. Bower, R.; Green, V.L.; Kuvshinova, E.; Kuvshinov, D.; Karsai, L.; Crank, S.T.; Stafford, N.D.; Greenman, J. Maintenance of head and neck tumor on-chip: Gateway to personalized treatment? Futur. Sci. OA 2017, 3, FSO174–FSO174. https://doi.org/10.4155/fsoa-2016-0089.91. Carr, S.D.; Green, V.L.; Stafford, N.D.; Greenman, J. Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices. Otolaryngol. Neck Surg. 2014, 150, 73–80. https://doi.org/10.1177/0194599813507427.92. Cheah, R.; Srivastava, R.; Stafford, N.D.; Beavis, A.W.; Green, V.; Greenman, J. Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy. Int. J. Oncol. 2017, 51, 1227–1238. https://doi.org/10.3892/ijo.2017.4118.93. Kennedy, R.; Kuvshinov, D.; Sdrolia, A.; Kuvshinova, E.; Hilton, K.; Crank, S.; Beavis, A.W.; Green, V.; Greenman, J. A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens. Sci. Rep. 2019, 9, 6327. https://doi.org/10.1038/s41598-019-42745-2.94. Sylvester, D.; Hattersley, S.M.; Stafford, N.D.; Haswell, S.J.; Greenman, J. Development of Microfluidic-based Analytical Methodology for Studying the Effects of Chemotherapy Agents on Cancer Tissue. Curr. Anal. Chem. 2012, 9, 2–8. https://doi.org/10.2174/157341113804486446.95. Hattersley, S.M.; Sylvester, D.C.; Dyer, C.E.; Stafford, N.D.; Haswell, S.J.; Greenman, J. A microfluidic system for testing the responses of head and neck squamous cell carcinoma tissue biopsies to treatment with chemotherapy drugs. Ann. Biomed. Eng. 2012, 40, 1277–1288. https://doi.org/10.1007/s10439-011-0428-9.96. Tinhofer, I.; Braunholz, D.; Klinghammer, K. Preclinical models of head and neck squamous cell carcinoma for a basic understanding of cancer biology and its translation into efficient therapies. Cancers Head Neck 2020, 5, 9. https://doi.org/10.1186/s41199-020-00056-4.97. Melissaridou, S.; Wiechec, E.; Magan, M.; Jain, M.V.; Chung, M.K.; Farnebo, L.; Roberg, K. The effect of 2D and 3D cell cultures on treatment response, EMT profile and stem cell features in head and neck cancer. Cancer Cell Int. 2019, 19, 16. https://doi.org/10.1186/s12935-019-0733-1.98. Mahmutović, L.; Bilajac, E.; Hromić-Jahjefendić, A. Meet the insidious players: Review of viral infections in head and neck cancer etiology with an update on clinical trials. Microorganisms 2021, 9, 1001. https://doi.org/10.3390/microorganisms9051001.99. Forslund, O.; Sugiyama, N.; Wu, C.; Ravi, N.; Jin, Y.; Swoboda, S.; Andersson, F.; Bzhalava, D.; Hultin, E.; Paulsson, K.; et al. A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin. BMC Cancer 2019, 19, 265. https://doi.org/10.1186/s12885-019-5469-8.100. Wegge, M.; Dok, R.; Dubois, L.J.; Nuyts, S. Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer. Int. J. Mol. Sci. 2023, 24, 3763. https://doi.org/10.3390/ijms24043763.101. Vitti, E.T.; Kacperek, A.; Parsons, J.L. Targeting DNA double-strand break repair enhances radiosensitivity of HPV-positive and HPV-negative head and neck squamous cell carcinoma to photons and protons. Cancers 2020, 12, 1490. https://doi.org/10.3390/cancers12061490.102. Bonartsev, A.P.; Lei, B.; Kholina, M.S.; Menshikh, K.A.; Svyatoslavov, D.S.; Samoylova, S.I.; Sinelnikov, M.Y.; Voinova, V.V.; Shaitan, K.V.; Kirpichnikov, M.P.; et al. Models of head and neck squamous cell carcinoma using bioengineering approaches. Crit. Rev. Oncol. 2022, 175, 103724. https://doi.org/10.1016/j.critrevonc.2022.103724103. Almela, T.; Tayebi, L.; Moharamzadeh, K. 3D bioprinting for in vitro models of oral cancer: Toward development and validation. Bioprinting 2021, 22, e00132. https://doi.org/10.1016/j.bprint.2021.e00132.104. Matuszczak, S.; Szczepanik, K.; Grządziel, A.; Drzyzga, A.; Cichoń, T.; Czapla, J.; Pilny, E.; Smolarczyk, R. The Effect of Radiotherapy on Cell Survival and Inflammatory Cytokine and Chemokine Secretion in a Co-Culture Model of Head and Neck Squamous Cell Carcinoma and Normal Cells. Biomedicines 2023, 11, 1773. https://doi.org/10.3390/biomedicines11061773.105. Ludwig, N.; Yerneni, S.S.; Razzo, B.M.; Whiteside, T.L. Exosomes from HNSCC promote angiogenesis through repro-gramming of endothelial cells. Mol. Cancer Res. 2018, 16, 1798–1808. https://doi.org/10.1158/1541-7786.mcr-18-0358.106. Choi, S.-Y.; Kang, S.H.; Oh, S.Y.; Lee, K.Y.; Lee, H.-J.; Gum, S.; Kwon, T.-G.; Kim, J.-W.; Lee, S.-T.; Hong, Y.J.; et al. Differential angiogenic potential of 3-dimension spheroid of hnscc cells in mouse xenograft. Int. J. Mol. Sci. 2021, 22, 8245. https://doi.org/10.3390/ijms22158245.107. Bessho, T.; Takagi, T.; Igawa, K.; Sato, K. Gelatin-based cell culture device for construction and X-ray irradiation of a three-dimensional oral cancer model. Anal. Sci. 2023, 39, 771–778. https://doi.org/10.1007/s44211-023-00308-6.108. Yang, J.; Wang, W.; Xia, H.; Yu, Z.; Li, H.; Ren, J.; Chen, G.; Wang, B.; Jia, J.; Zhang, W.; et al. Lymphotoxin-α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3-dependent manner. Int. J. Cancer 2019, 145, 1358–1370. https://doi.org/10.1002/ijc.32221.109. Gilazieva, Z.; Ponomarev, A.; Rutland, C.; Rizvanov, A.; Solovyeva, V. Promising applications of tumor spheroids and organoids for personalized medicine. Cancers 2020, 12, 2727. https://doi.org/10.3390/cancers12102727.110. Ehsan, S.M.; Welch-Reardon, K.M.; Waterman, M.L.; Hughes, C.C.W.; George, S.C. A three-dimensional in vitro model of tumor cell intravasation. Integr. Biol. 2014, 6, 603–610. https://doi.org/10.1039/c3ib40170g.111. Buchanan, C.F.; Verbridge, S.S.; Vlachos, P.P.; Rylander, M.N. Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model. Cell Adhes. Migr. 2014, 8, 517–524. https://doi.org/10.4161/19336918.2014.970001.112. Cauli, E.; Polidoro, M.A.; Marzorati, S.; Bernardi, C.; Rasponi, M.; Lleo, A. Cancer-on-chip: A 3D model for the study of the tumor microenvironment. J. Biol. Eng. 2023, 17, 53. https://doi.org/10.1186/s13036-023-00372-6.113. Clarke, R. Introduction: Cancer Systems and Integrative Biology; Humana: New York, NY, USA, 2023; Volume 2660. https://doi.org/10.1007/978-1-0716-3163-8_1.114. Tuomainen, K.; Al-Samadi, A.; Potdar, S.; Turunen, L.; Turunen, M.; Karhemo, P.-R.; Bergman, P.; Risteli, M.; Åström, P.; Tiikkaja, R.; et al. Human tumor–derived matrix improves the predictability of head and neck cancer drug testing. Cancers 2020, 12, 92. https://doi.org/10.3390/cancers12010092.115. Naakka, E.; Wahbi, W.; Tiikkaja, R.; Juurikka, K.; Sandvik, T.; Koivunen, P.; Autio, T.; Tikanto, J.; Väisänen, J.; Tuominen, H.; et al. Novel human lymph node-derived matrix supports the adhesion of metastatic oral carcinoma cells. BMC Cancer 2023, 23, 750. https://doi.org/10.1186/s12885-023-11275-6.116. Drost, J.; Clevers, H. Organoids in cancer research. Nat. Rev. Cancer 2018, 18, 407–418. https://doi.org/10.1038/s41568-018-0007-6.117. Pillai, S.; Kwan, J.C.; Yaziji, F.; Yu, H.; Tran, S.D. Mapping the Potential of Microfluidics in Early Diagnosis and Per-sonalized Treatment of Head and Neck Cancers. Cancers 2023, 15, 3894. https://doi.org/10.3390/cancers15153894.118. Sawant, S.; Dongre, H.; Singh, A.K.; Joshi, S.; Costea, D.E.; Mahadik, S.; Ahire, C.; Makani, V.; Dange, P.; Sharma, S.; et al. Establishment of 3D co-culture models from different stages of human tongue tumorigenesis: Utility in understanding neoplastic progression. PLoS ONE 2016, 11, e0160615. https://doi.org/10.1371/journal.pone.0160615.119. Millen, R.; De Kort, W.W.; Koomen, M.; van Son, G.J.; Gobits, R.; de Vries, B.P.; Begthel, H.; Zandvliet, M.; Doornaert, P.; Raaijmakers, C.P.; et al. Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification. Med 2023, 4, 290–310.e12. https://doi.org/10.1016/j.medj.2023.04.003.120. Establishment of Squamous Cell Organoids of the Head and Neck to Assess Their Response to Innovative Therapies (ORGAVADS); ClinicalTrials.gov Identifier: NCT04261192.121. Selecting Chemotherapy with High-throughput Drug Screen Assay Using Patient Derived Organoids in Patients with Refractory Solid Tumours (SCORE); ClinicalTrials.gov Identifier: NCT04279509.122. SOTO: Treatment Sensitivity of Organoids to Predict Treatment Outcome; ClinicalTrials.gov Identifier: NCT05400239.
  2. Johnson, D.E.; Burtness, B.; Leemans, C.R.; Lui, V.W.Y.; Bauman, J.E.; Grandis, J.R. Head and neck squamous cell carcinoma. Nat. Rev. Dis. Primers 2020, 6, 92.
  3. Nissi, L.; Suilamo, S.; Kytö, E.; Vaittinen, S.; Irjala, H.; Minn, H. Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume. Clin. Transl. Radiat. Oncol. 2021, 27, 139–146.
  4. Boguszewicz, Ł. Predictive Biomarkers for Response and Toxicity of Induction Chemotherapy in Head and Neck Cancers. Front. Oncol. 2022, 12, 900903.
  5. Schanne, D.H.; Koch, A.; Elicin, O.; Giger, R.; Medová, M.; Zimmer, Y.; Aebersold, D.M. Prognostic and Predictive Biomarkers in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy—A Systematic Review. Biomedicines 2022, 10, 3288.
  6. Budach, V.; Tinhofer, I. Novel prognostic clinical factors and biomarkers for outcome prediction in head and neck cancer: A systematic review. Lancet Oncol. 2019, 20, e313–e326.
  7. Easty, D.M.; Easty, G.C.; Carter, R.L.; Monaghan, P.; Butler, L.J. Ten human carcinoma cell lines derived from squamous carcinomas of the head and neck. Br. J. Cancer 1981, 43, 772–785.
  8. Chaves, P.; Garrido, M.; Oliver, J.; Pérez-Ruiz, E.; Barragan, I.; Rueda-Domínguez, A. Preclinical models in head and neck squamous cell carcinoma. Br. J. Cancer 2023, 128, 1819–1827.
  9. Lepikhova, T.; Karhemo, P.-R.; Louhimo, R.; Yadav, B.; Murumägi, A.; Kulesskiy, E.; Kivento, M.; Sihto, H.; Grénman, R.; Syrjänen, S.M.; et al. Drug-sensitivity screening and genomic characterization of 45 hpV-negative head and neck carcinoma cell lines for novel biomarkers of drug efficacy. Mol. Cancer Ther. 2018, 17, 2060–2071.
  10. Greaney-Davies, F.S.; Risk, J.M.; Robinson, M.; Liloglou, T.; Shaw, R.J.; Schache, A.G. Essential characterisation of human papillomavirus positive head and neck cancer cell lines. Oral Oncol. 2020, 103, 104613.
  11. Lin, C.J.; Grandis, J.R.; Carey, T.E.; Gollin, S.M.; Whiteside, T.L.; Koch, W.M.; Ferris, R.L.; Lai, S.Y. Head and neck squamous cell carcinoma cell lines: Established models and rationale for selection. Head Neck 2007, 29, 163–188.
  12. Close, D.A.; Wang, A.X.; Kochanek, S.J.; Shun, T.; Eiseman, J.L.; Johnston, P.A. Implementation of the NCI-60 Human Tumor Cell Line Panel to Screen 2260 Cancer Drug Combinations to Generate >3 Million Data Points Used to Populate a Large Matrix of Anti-Neoplastic Agent Combinations (ALMANAC) Database. SLAS Discov. Adv. Sci. Drug Discov. 2019, 24, 242–263.
  13. American Type Culture Collection. Head and Neck Cancer Panel TCP-1012TM. In Medical Radiology; Springer: Cham, Switzerland, 2022; pp. 137–157.
  14. Zhao, M.; Sano, D.; Pickering, C.R.; Jasser, S.A.; Henderson, Y.C.; Clayman, G.L.; Sturgis, E.M.; Ow, T.J.; Lotan, R.; Carey, T.; et al. Assembly and initial characterization of a panel of 85 genomically validated cell lines from diverse head and neck tumor sites. Clin. Cancer Res. 2011, 17, 7248–7264.
  15. Li, H.; Wawrose, J.S.; Gooding, W.E.; Garraway, L.A.; Lui, V.W.Y.; Peyser, N.D.; Grandis, J.R. Genomic analysis of head and neck squamous cell carcinoma cell lines and human tumors: A rational approach to preclinical model selection. Mol. Cancer Res. 2014, 12, 571–582.
  16. Kapałczyńska, M.; Kolenda, T.; Przybyła, W.; Zajączkowska, M.; Teresiak, A.; Filas, V.; Ibbs, M.; Bliźniak, R.; Łuczewski, L.; Lamperska, K. 2D and 3D cell cultures—A comparison of different types of cancer cell cultures. Arch. Med. Sci. 2018, 14, 910–919.
  17. Mseka, T.; Bamburg, J.R.; Cramer, L.P. ADF/cofilin family proteins control formation of oriented actin-filament bundles in the cell body to trigger fibroblast polarization. J. Cell Sci. 2007, 120, 4332–4344.
  18. Li, C.; Kato, M.; Shiue, L.; Shively, J.E.; Ares, M.; Lin, R.-J. Cell type and culture condition-dependent alternative splicing in human breast cancer cells revealed by splicing-sensitive microarrays. Cancer Res 2006, 66, 1990–1999.
  19. Seliger, B.; Al-Samadi, A.; Yang, B.; Salo, T.; Wickenhauser, C. In vitro models as tools for screening treatment options of head and neck cancer. Front. Med. 2022, 9, 971726.
  20. Burford-Mason, A.P.; Irish, J.C.; MacKay, A.J.; Gullane, P.J.; Bassett, R.; Dardick, I. Squamous cell carcinomas of the head and neck cultured in floating collagen gels: 1. The maintenance of stromal and epithelial elements in vitro without fibroblast overgrowth. Otolaryngol. Neck Surg. 1997, 116, 213–222.
  21. Jubelin, C.; Muñoz-Garcia, J.; Griscom, L.; Cochonneau, D.; Ollivier, E.; Heymann, M.-F.; Vallette, F.M.; Oliver, L.; Heymann, D. Three-dimensional in vitro culture models in oncology research. Cell Biosci. 2022, 12, 155.
  22. Cekanova, M.; Rathore, K. Animal models and therapeutic molecular targets of cancer: Utility and limitations. Drug Des. Dev. Ther. 2014, 8, 1911–1922.
  23. Ghosh, S.; Prasad, M.; Kundu, K.; Cohen, L.; Yegodayev, K.M.; Zorea, J.; Joshua, B.-Z.; Lasry, B.; Dimitstein, O.; Bahat-Dinur, A.; et al. Tumor tissue explant culture of patient-derived xenograft as potential prioritization tool for targeted therapy. Front. Oncol. 2019, 9, 17.
  24. Breslin, S.; O’driscoll, L. The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance. Oncotarget 2016, 7, 45745–45756.
  25. Park, S.-B.; Jung, W.K.; Kim, H.R.; Yu, H.-Y.; Kim, Y.H.; Kim, J. Esculetin has therapeutic potential via the proapoptotic signaling pathway in A253 human submandibular salivary gland tumor cells. Exp. Ther. Med. 2022, 24, 533.
  26. Colley, H.E.; Hearnden, V.; Jones, A.V.; Weinreb, P.H.; Violette, S.M.; MacNeil, S.; Thornhill, M.H.; Murdoch, C. Development of tissue-engineered models of oral dysplasia and early invasive oral squamous cell carcinoma. Br. J. Cancer 2011, 105, 1582–1592.
  27. Bernhard, W.; Barreto, K.; El-Sayed, A.; DeCoteau, J.; Geyer, C.R. Imaging Immune Cells Using Fc Domain Probes in Mouse Cancer Xenograft Models. Cancers 2022, 14, 300.
  28. Bernareggi, D.; Xie, Q.; Prager, B.C.; Yun, J.; Cruz, L.S.; Pham, T.V.; Kim, W.; Lee, X.; Coffey, M.; Zalfa, C.; et al. CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity. Nat. Commun. 2022, 13, 1899.
  29. Hsu, C.-M.; Yang, M.-Y.; Tsai, M.-S.; Chang, G.-H.; Yang, Y.-H.; Tsai, Y.-T.; Wu, C.-Y.; Chang, S.-F. Dihydroisotanshinone i as a treatment option for head and neck squamous cell carcinomas. Int. J. Mol. Sci. 2021, 22, 8881.
  30. Tevlek, A.; Kecili, S.; Ozcelik, O.S.; Kulah, H.; Tekin, H.C. Spheroid Engineering in Microfluidic Devices. ACS Omega 2023, 8, 3630–3649.
  31. Huo, K.-G.; D’arcangelo, E.; Tsao, M.-S. Patient-derived cell line, xenograft and organoid models in lung cancer therapy. Transl. Lung Cancer Res. 2020, 9, 2214–2232.
  32. Moya-Garcia, C.R.; Okuyama, H.; Sadeghi, N.; Li, J.; Tabrizian, M.; Li-Jessen, N.Y.K. In vitro models for head and neck cancer: Current status and future perspective. Front. Oncol. 2022, 12, 960340.
  33. Morrissey, B.; Blyth, K.; Carter, P.; Chelala, C.; Jones, L.; Holen, I.; Speirs, V. The Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) Framework: Encouraging Reduction, Replacement, and Refinement in Animal Research. PLoS Biol. 2017, 15, e2000719.
  34. Tenschert, E.; Kern, J.; Affolter, A.; Rotter, N.; Lammert, A. Optimisation of Conditions for the Formation of Spheroids of Head and Neck Squamous Cell Carcinoma Cell Lines for Use as Animal Alternatives. Altern. Lab. Anim. 2022, 50, 414–422.
  35. Mehta, G.; Hsiao, A.Y.; Ingram, M.; Luker, G.D.; Takayama, S. Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J. Control. Release 2012, 164, 192–204.
  36. Elliott, N.T.; Yuan, F. A review of three-dimensional in vitro tissue models for drug discovery and transport studies. J. Pharm. Sci. 2011, 100, 59–74.
  37. Kimlin, L.C.; Casagrande, G.; Virador, V.M. In vitro three-dimensional (3D) models in cancer research: An update. Mol. Carcinog. 2013, 52, 167–182.
  38. Jung, A.R.; Jung, C.-H.; Noh, J.K.; Lee, Y.C.; Eun, Y.-G. Epithelial-mesenchymal transition gene signature is associated with prognosis and tumor microenvironment in head and neck squamous cell carcinoma. Sci. Rep. 2020, 10, 3652.
  39. Han, S.J.; Kwon, S.; Kim, K.S. Challenges of applying multicellular tumor spheroids in preclinical phase. Cancer Cell Int. 2021, 21, 152.
  40. Costa, E.C.; Moreira, A.F.; De Melo-Diogo, D.; Gaspar, V.M.; Carvalho, M.P.; Correia, I.J. 3D tumor spheroids: An overview on the tools and techniques used for their analysis. Biotechnol. Adv. 2016, 34, 1427–1441.
  41. Thakuri, P.S.; Gupta, M.; Plaster, M.; Tavana, H. Quantitative Size-Based Analysis of Tumor Spheroids and Responses to Therapeutics. ASSAY Drug Dev. Technol. 2019, 17, 140–149.
  42. Cui, X.; Hartanto, Y.; Zhang, H. Advances in multicellular spheroids formation. J. R. Soc. Interface 2017, 14, 20160877.
  43. Zanoni, M.; Cortesi, M.; Zamagni, A.; Arienti, C.; Pignatta, S.; Tesei, A. Modeling neoplastic disease with spheroids and organoids. J. Hematol. Oncol. 2020, 13, 97.
  44. Huang, B.-W.; Gao, J.-Q. Application of 3D cultured multicellular spheroid tumor models in tumor-targeted drug delivery system research. J. Control. Release 2018, 270, 246–259.
  45. Lu, H.; Stenzel, M.H. Multicellular Tumor Spheroids (MCTS) as a 3D In Vitro Evaluation Tool of Nanoparticles. Small 2018, 14, e1702858.
  46. Lin, R.; Chang, H. Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol. J. 2008, 3, 1172–1184.
  47. Raghavan, S.; Mehta, P.; Horst, E.N.; Ward, M.R.; Rowley, K.R.; Mehta, G. Comparative analysis of tumor spheroid generation techniques for differential in vitro drug toxicity. Oncotarget 2016, 7, 16948–16961.
  48. Luoto, K.R.; Kumareswaran, R.; Bristow, R.G. Tumor hypoxia as a driving force in genetic instability. Genome Integr. 2013, 4, 5.
  49. Das, V.; Bruzzese, F.; Konečný, P.; Iannelli, F.; Budillon, A.; Hajdúch, M. Pathophysiologically relevant in vitro tumor models for drug screening. Drug Discov. Today 2015, 20, 848–855.
  50. Yasui, H.; Kawai, T.; Matsumoto, S.; Saito, K.; Devasahayam, N.; Mitchell, J.B.; Camphausen, K.; Inanami, O.; Krishna, M.C. Quantitative imaging of pO2 in orthotopic murine gliomas: Hypoxia correlates with resistance to radiation. Free. Radic. Res. 2017, 51, 861–871.
  51. Gatenby, R.A.; Gillies, R.J. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 2004, 4, 891–899.
  52. Kelm, J.M.; Fussenegger, M. Microscale tissue engineering using gravity-enforced cell assembly. Trends Biotechnol. 2004, 22, 195–202.
  53. Friedrich, J.; Ebner, R.; Kunz-Schughart, L.A. Experimental anti-tumor therapy in 3-D: Spheroids—Old hat or new challenge? Int. J. Radiat. Biol. 2007, 83, 849–871.
  54. Friedrich, J.; Seidel, C.; Ebner, R.; Kunz-Schughart, L.A. Spheroid-based drug screen: Considerations and practical approach. Nat. Protoc. 2009, 4, 309–324.
  55. Ham, S.L.; Joshi, R.; Thakuri, P.S.; Tavana, H. Liquid-based three-dimensional tumor models for cancer research and drug discovery. Exp. Biol. Med. 2016, 241, 939–954.
  56. Santi, M.; Mapanao, A.K.; Cappello, V.; Voliani, V. Production of 3D tumor models of head and neck squamous cell carcinomas for nanotheranostics assessment. ACS Biomater. Sci. Eng. 2020, 6, 4862–4869.
  57. Ivascu, A.; Kubbies, M. Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis. J Biomol. Screen. 2006, 11, 922–932.
  58. Tevis, K.M.; Colson, Y.L.; Grinstaff, M.W. Embedded Spheroids as Models of the Cancer Microenvironment. Adv. Biosyst. 2017, 1, 1700083.
  59. Hagemann, J.; Jacobi, C.; Gstoettner, S.; Welz, C.; Schwenk-Zieger, S.; Stauber, R.; Strieth, S.; Kuenzel, J.; Baumeister, P.; Becker, S. Therapy testing in a spheroid-based 3D cell culture model for head and neck squamous cell carcinoma. J. Vis. Exp. 2018, 2018, e57012.
  60. Shao, S.; Scholtz, L.U.; Gendreizig, S.; Martínez-Ruiz, L.; Florido, J.; Escames, G.; Schürmann, M.; Hain, C.; Hose, L.; Mentz, A.; et al. Primary head and neck cancer cell cultures are susceptible to proliferation of Epstein-Barr virus infected lymphocytes. BMC Cancer 2023, 23, 47.
  61. Hagemann, J.; Jacobi, C.; Hahn, M.; Schmid, V.; Welz, C.; Schwenk-Zieger, S.; Stauber, R.; Baumeister, P.; Becker, S. Spheroid-based 3D cell cultures enable personalized therapy testing and drug discovery in head and neck cancer. Anticancer. Res. 2017, 37, 2201–2210.
  62. Vakhshiteh, F.; Bagheri, Z.; Soleimani, M.; Ahvaraki, A.; Pournemat, P.; Alavi, S.E.; Madjd, Z. Heterotypic tumor spheroids: A platform for nanomedicine evaluation. J. Nanobiotechnol. 2023, 21, 249.
  63. Antoni, D.; Burckel, H.; Josset, E.; Noel, G. Three-dimensional cell culture: A breakthrough in vivo. Int. J. Mol. Sci. 2015, 16, 5517–5527.
  64. Kobayashi, H.; Man, S.; Graham, C.H.; Kapitain, S.J.; Teicher, B.A.; Kerbel, R.S. Acquired multicellular-mediated resistance to alkylating agents in cancer. Proc. Natl. Acad. Sci. USA 1993, 90, 3294–3298.
  65. He, Y.; Deng, P.; Yan, Y.; Zhu, L.; Chen, H.; Li, T.; Li, Y.; Li, J. Matrisome provides a supportive microenvironment for oral squamous cell carcinoma progression. J. Proteom. 2022, 253, 104454.
  66. Anbazhagan, R.; Sakakura, T.; Gusterson, B.A. The distribution of immuno-reactive tenascin in the epithelial-mesenchymal junctional areas of benign and malignant squamous epithelia. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 1990, 59, 59–63.
  67. Berndt, A.; Hyckel, P.; Kosmehl, H.; Könneker, A. Dreidimensionales In-vitro-Invasionsmodell für orale Plattenepithelkarzinome. Mund-Kiefer-und Gesichtschirurgie 1998, 2, 256–260.
  68. Fischbach, C.; Chen, R.; Matsumoto, T.; Schmelzle, T.; Brugge, J.S.; Polverini, P.J.; Mooney, D.J. Engineering tumors with 3D scaffolds. Nat. Methods 2007, 4, 855–860.
  69. Rossi, L.; Corvò, R.; Videtic, G.M.; Paulus, R.; Singh, A.K.; Chang, J.Y.; Parker, W.; Olivier, K.R.; Timmerman, R.D.; Komaki, R.R.; et al. Retinoic acid modulates the radiosensitivity of head-and-neck squamous carcinoma cells grown in collagen gel. Int. J. Radiat. Oncol. 2002, 53, 1319–1327.
  70. Miserocchi, G.; Cocchi, C.; De Vita, A.; Liverani, C.; Spadazzi, C.; Calpona, S.; Di Menna, G.; Bassi, M.; Meccariello, G.; De Luca, G.; et al. Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas. Cancer Biol. Med. 2021, 18, 502–516.
  71. Gu, C.; Zhang, Y.; Chen, D.; Liu, H.; Mi, K. Tunicamycin-induced endoplasmic reticulum stress inhibits chemoresistance of FaDu hypopharyngeal carcinoma cells in 3D collagen I cultures and in vivo. Exp. Cell Res. 2021, 405, 112725.
  72. Young, M.; Rodenhizer, D.; Dean, T.; D’Arcangelo, E.; Xu, B.; Ailles, L.; McGuigan, A.P. A TRACER 3D Co-Culture tumour model for head and neck cancer. Biomaterials 2018, 164, 54–69.
  73. Dean, T.; Li, N.T.; Cadavid, J.L.; Ailles, L.; McGuigan, A.P. A TRACER culture invasion assay to probe the impact of cancer associated fibroblasts on head and neck squamous cell carcinoma cell invasiveness. Biomater. Sci. 2020, 8, 3078–3094.
  74. Ricci, C.; Moroni, L.; Danti, S. Cancer tissue engineering new perspectives in understanding the biology of solid tumours a critical review. OA Tissue Eng. 2013, 1, 1–7.
  75. Wang, J.-Z.; Zhu, Y.-X.; Ma, H.-C.; Chen, S.-N.; Chao, J.-Y.; Ruan, W.-D.; Wang, D.; Du, F.-G.; Meng, Y.-Z. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. Mater. Sci. Eng. C 2016, 62, 215–225.
  76. Curvello, R.; Kast, V.; Ordóñez-Morán, P.; Mata, A.; Loessner, D. Biomaterial-based platforms for tumour tissue engineering. Nat. Rev. Mater. 2023, 8, 314–330.
  77. Villasante, A.; Vunjak-Novakovic, G. Tissue-engineered models of human tumors for cancer research. Expert Opin. Drug Discov. 2015, 10, 257–268.
  78. Gu, Y.; Schwarz, B.; Forget, A.; Barbero, A.; Martin, I.; Shastri, V.P. Advanced bioink for 3D bioprinting of complex free-standing structures with high stiffness. Bioengineering 2020, 7, 141.
  79. Zhang, Y.S.; Duchamp, M.; Oklu, R.; Ellisen, L.W.; Langer, R.; Khademhosseini, A. Bioprinting the Cancer Microenvironment. ACS Biomater. Sci. Eng. 2016, 2, 1710–1721.
  80. Murphy, S.V.; Atala, A. 3D bioprinting of tissues and organs. Nat. Biotechnol. 2014, 32, 773–785.
  81. Hoarau-Véchot, J.; Rafii, A.; Touboul, C.; Pasquier, J. Halfway between 2D and animal models: Are 3D cultures the ideal tool to study cancer-microenvironment interactions? Int. J. Mol. Sci. 2018, 19, 181.
  82. Zhang, Y.S.; Yue, K.; Aleman, J.; Mollazadeh-Moghaddam, K.; Bakht, S.M.; Yang, J.; Jia, W.; Dell’erba, V.; Assawes, P.; Shin, S.R.; et al. 3D Bioprinting for Tissue and Organ Fabrication. Ann. Biomed. Eng. 2017, 45, 148–163.
  83. Boland, T.; Xu, T.; Damon, B.; Cui, X. Application of inkjet printing to tissue engineering. Biotechnol. J. 2006, 1, 910–917.
  84. Chang, C.C.; Boland, E.D.; Williams, S.K.; Hoying, J.B. Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies. J. Biomed. Mater. Res. Part B Appl. Biomater. 2011, 98B, 160–170.
  85. Guillotin, B.; Souquet, A.; Catros, S.; Duocastella, M.; Pippenger, B.; Bellance, S.; Bareille, R.; Rémy, M.; Bordenave, L.; Amédée, J.; et al. Laser assisted bioprinting of engineered tissue with high cell density and microscale organization. Biomaterials 2010, 31, 7250–7256.
  86. Ma, X.; Qu, X.; Zhu, W.; Li, Y.; Yuan, S.; Zhang, H.; Liu, J.; Wang, P.; Lai, C.S.E.; Zanella, F.; et al. Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proc. Natl. Acad. Sci. USA 2016, 113, 2206–2211.
  87. Nie, J.; Gao, Q.; Fu, J.; He, Y. Grafting of 3D Bioprinting to In Vitro Drug Screening: A Review. Adv. Healthc. Mater. 2020, 9, e1901773.
  88. Kort-Mascort, J.; Bao, G.; Elkashty, O.; Flores-Torres, S.; Munguia-Lopez, J.G.; Jiang, T.; Ehrlicher, A.J.; Mongeau, L.; Tran, S.D.; Kinsella, J.M. Decellularized Extracellular Matrix Composite Hydrogel Bioinks for the Development of 3D Bioprinted Head and Neck in Vitro Tumor Models. ACS Biomater. Sci. Eng. 2021, 7, 5288–5300.
  89. Kort-Mascort, J.; Shen, M.L.; Martin, E.; Flores-Torres, S.; Pardo, L.A.; Siegel, P.M.; Tran, S.D.; Kinsella, J.M. Bioprinted cancer-stromal in-vitro models in a decellularized ECM-based bioink exhibit progressive remodeling and maturation. Biomed. Mater. 2023, 18, 045022.
  90. Saglam-Metiner, P.; Gulce-Iz, S.; Biray-Avci, C. Bioengineering-inspired three-dimensional culture systems: Organoids to create tumor microenvironment. Gene 2019, 686, 203–212.
  91. Barbet, V.; Broutier, L. Future Match Making: When Pediatric Oncology Meets Organoid Technology. Front. Cell Dev. Biol. 2021, 9, 674219.
  92. Kim, S.; Choung, S.; Sun, R.X.; Ung, N.; Hashemi, N.; Fong, E.J.; Lau, R.; Spiller, E.; Gasho, J.; Foo, J.; et al. Comparison of Cell and Organoid-Level Analysis of Patient-Derived 3D Organoids to Evaluate Tumor Cell Growth Dynamics and Drug Response. SLAS Discov. Adv. Sci. Drug Discov. 2020, 25, 744–754.
  93. Clevers, H. Modeling Development and Disease with Organoids. Cell 2016, 165, 1586–1597.
  94. Papaccio, F.; Cabeza-Segura, M.; Garcia-Micò, B.; Tarazona, N.; Roda, D.; Castillo, J.; Cervantes, A. Will Organoids Fill the Gap towards Functional Precision Medicine? J. Pers. Med. 2022, 12, 1939.
  95. Yan, H.H.N.; Siu, H.C.; Law, S.; Ho, S.L.; Yue, S.S.K.; Tsui, W.Y.; Chan, D.; Chan, A.S.; Ma, S.; Lam, K.O.; et al. A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening. Cell Stem Cell 2018, 23, 882–897.e811.
  96. Driehuis, E.; Kretzschmar, K.; Clevers, H. Establishment of patient-derived cancer organoids for drug-screening applications. Nat. Protoc. 2020, 15, 3380–3409.
  97. Hughes, C.S.; Postovit, L.M.; Lajoie, G.A. Matrigel: A complex protein mixture required for optimal growth of cell culture. Proteomics 2010, 10, 1886–1890.
  98. Kaur, S.; Kaur, I.; Rawal, P.; Tripathi, D.M.; Vasudevan, A. Non-matrigel scaffolds for organoid cultures. Cancer Lett. 2021, 504, 58–66.
  99. Kozlowski, M.T.; Crook, C.J.; Ku, H.T. Towards organoid culture without Matrigel. Commun. Biol. 2021, 4, 1387.
  100. Gunti, S.; Hoke, A.T.K.; Vu, K.; London, N.R. Organoid and spheroid tumor models: Techniques and applications. Cancers 2021, 13, 874.
  101. Wang, X.-W.; Xia, T.-L.; Tang, H.-C.; Liu, X.; Han, R.; Zou, X.; Zhao, Y.-T.; Chen, M.-Y.; Li, G. Establishment of a patient-derived organoid model and living biobank for nasopharyngeal carcinoma. Ann. Transl. Med. 2022, 10, 526.
  102. Tuveson, D.A.; Clevers, H. Cancer modeling meets human organoid technology. Science 2019, 364, 952–955.
  103. Driehuis, E.; Kolders, S.; Spelier, S.; Lõhmussaar, K.; Willems, S.M.; Devriese, L.A.; de Bree, R.; de Ruiter, E.J.; Korving, J.; Begthel, H.; et al. Oral mucosal organoids as a potential platform for personalized cancer therapy. Cancer Discov. 2019, 9, 852–871.
  104. Kijima, T.; Nakagawa, H.; Shimonosono, M.; Chandramouleeswaran, P.M.; Hara, T.; Sahu, V.; Kasagi, Y.; Kikuchi, O.; Tanaka, K.; Giroux, V.; et al. Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells. Cell. Mol. Gastroenterol. Hepatol. 2019, 7, 73–91.
  105. Tanaka, N.; Osman, A.A.; Takahashi, Y.; Lindemann, A.; Patel, A.A.; Zhao, M.; Takahashi, H.; Myers, J.N. Head and neck cancer organoids established by modification of the CTOS method can be used to predict in vivo drug sensitivity. Oral Oncol. 2018, 87, 49–57.
  106. Zhao, H.; Hu, C.-Y.; Chen, W.-M.; Huang, P. Lactate Promotes Cancer Stem-like Property of Oral Sequamous Cell Carcinoma. Curr. Med. Sci. 2019, 39, 403–409.
  107. Lee, T.W.; Lai, A.; Harms, J.K.; Singleton, D.C.; Dickson, B.D.; Macann, A.M.J.; Hay, M.P.; Jamieson, S.M.F. Patient-derived xenograft and organoid models for precision medicine targeting of the tumour microenvironment in head and neck cancer. Cancers 2020, 12, 3743.
  108. Bonartsev, A.P.; Lei, B.; Kholina, M.S.; Menshikh, K.A.; Svyatoslavov, D.S.; Samoylova, S.I.; Sinelnikov, M.Y.; Voinova, V.V.; Shaitan, K.V.; Kirpichnikov, M.P.; et al. Models of head and neck squamous cell carcinoma using bioengineering approaches. Crit. Rev. Oncol. 2022, 175, 103724.
  109. Verduin, M.; Hoeben, A.; De Ruysscher, D.; Vooijs, M. Patient-Derived Cancer Organoids as Predictors of Treatment Response. Front. Oncol. 2021, 11, 820.
  110. Vlachogiannis, G.; Hedayat, S.; Vatsiou, A.; Jamin, Y.; Fernández-Mateos, J.; Khan, K.; Lampis, A.; Eason, K.; Huntingford, I.; Burke, R.; et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 2018, 359, 920–926.
  111. Yao, Y.; Xu, X.; Yang, L.; Zhu, J.; Wan, J.; Shen, L.; Xia, F.; Fu, G.; Deng, Y.; Pan, M.; et al. Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer. Cell Stem Cell 2020, 26, 17–26.E16.
  112. Park, M.; Kwon, J.; Kong, J.; Moon, S.M.; Cho, S.; Yang, K.Y.; Jang, W.I.; Kim, M.S.; Kim, Y.; Shin, U.S. A patient-derived organoid-based radiosensitivity model for the prediction of radiation responses in patients with rectal cancer. Cancers 2021, 13, 3760.
  113. Smith, R.C.; Tabar, V. Constructing and Deconstructing Cancers using Human Pluripotent Stem Cells and Organoids. Cell Stem Cell 2019, 24, 12–24.
  114. Wu, K.Z.; Adine, C.; Mitriashkin, A.; Aw, B.J.J.; Iyer, N.G.; Fong, E.L.S. Making In Vitro Tumor Models Whole Again. Adv. Healthc. Mater. 2023, 12, e2202279.
  115. Engelmann, L.; Thierauf, J.; Laureano, N.K.; Stark, H.-J.; Prigge, E.-S.; Horn, D.; Freier, K.; Grabe, N.; Rong, C.; Federspil, P.; et al. Organotypic co-cultures as a novel 3d model for head and neck squamous cell carcinoma. Cancers 2020, 12, 2330.
  116. Dohmen, A.J.; Sanders, J.; Canisius, S.; Jordanova, E.S.; Aalbersberg, E.A.; Brekel, M.W.v.D.; Neefjes, J.; Zuur, C.L. Sponge-supported cultures of primary head and neck tumors for an optimized preclinical model. Oncotarget 2018, 9, 25034–25047.
  117. Lee, J.; You, J.H.; Shin, D.; Roh, J.-L. Ex vivo culture of head and neck cancer explants in cell sheet for testing chemotherapeutic sensitivity. J. Cancer Res. Clin. Oncol. 2020, 146, 2497–2507.
  118. Demers, I.; Donkers, J.; Kremer, B.; Speel, E.J. Ex Vivo Culture Models to Indicate Therapy Response in Head and Neck Squamous Cell Carcinoma. Cells 2020, 9, 2527.
  119. Peria, M.; Donnadieu, J.; Racz, C.; Ikoli, J.; Galmiche, A.; Chauffert, B.; Page, C. Evaluation of individual sensitivity of head and neck squamous cell carcinoma to cetuximab by short-term culture of tumor slices. Head Neck 2016, 38, E911–E915.
  120. Gerlach, M.M.; Merz, F.; Wichmann, G.; Kubick, C.; Wittekind, C.; Lordick, F.; Dietz, A.; Bechmann, I. Slice cultures from head and neck squamous cell carcinoma: A novel test system for drug susceptibility and mechanisms of resistance. Br. J. Cancer 2014, 110, 479–488.
  121. Bower, R.; Green, V.L.; Kuvshinova, E.; Kuvshinov, D.; Karsai, L.; Crank, S.T.; Stafford, N.D.; Greenman, J. Maintenance of head and neck tumor on-chip: Gateway to personalized treatment? Futur. Sci. OA 2017, 3, FSO174.
  122. Mahmutović, L.; Bilajac, E.; Hromić-Jahjefendić, A. Meet the insidious players: Review of viral infections in head and neck cancer etiology with an update on clinical trials. Microorganisms 2021, 9, 1001.
  123. Forslund, O.; Sugiyama, N.; Wu, C.; Ravi, N.; Jin, Y.; Swoboda, S.; Andersson, F.; Bzhalava, D.; Hultin, E.; Paulsson, K.; et al. A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin. BMC Cancer 2019, 19, 265.
  124. Wegge, M.; Dok, R.; Dubois, L.J.; Nuyts, S. Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer. Int. J. Mol. Sci. 2023, 24, 3763.
  125. Vitti, E.T.; Kacperek, A.; Parsons, J.L. Targeting DNA double-strand break repair enhances radiosensitivity of HPV-positive and HPV-negative head and neck squamous cell carcinoma to photons and protons. Cancers 2020, 12, 1490.
  126. Millen, R.; De Kort, W.W.; Koomen, M.; van Son, G.J.; Gobits, R.; de Vries, B.P.; Begthel, H.; Zandvliet, M.; Doornaert, P.; Raaijmakers, C.P.; et al. Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification. Med 2023, 4, 290–310.e12.
  127. Almela, T.; Tayebi, L.; Moharamzadeh, K. 3D bioprinting for in vitro models of oral cancer: Toward development and validation. Bioprinting 2021, 22, e00132.
  128. Matuszczak, S.; Szczepanik, K.; Grządziel, A.; Drzyzga, A.; Cichoń, T.; Czapla, J.; Pilny, E.; Smolarczyk, R. The Effect of Radiotherapy on Cell Survival and Inflammatory Cytokine and Chemokine Secretion in a Co-Culture Model of Head and Neck Squamous Cell Carcinoma and Normal Cells. Biomedicines 2023, 11, 1773.
  129. Ludwig, N.; Yerneni, S.S.; Razzo, B.M.; Whiteside, T.L. Exosomes from HNSCC promote angiogenesis through reprogramming of endothelial cells. Mol. Cancer Res. 2018, 16, 1798–1808.
  130. Choi, S.-Y.; Kang, S.H.; Oh, S.Y.; Lee, K.Y.; Lee, H.-J.; Gum, S.; Kwon, T.-G.; Kim, J.-W.; Lee, S.-T.; Hong, Y.J.; et al. Differential angiogenic potential of 3-dimension spheroid of hnscc cells in mouse xenograft. Int. J. Mol. Sci. 2021, 22, 8245.
  131. Yang, J.; Wang, W.; Xia, H.; Yu, Z.; Li, H.; Ren, J.; Chen, G.; Wang, B.; Jia, J.; Zhang, W.; et al. Lymphotoxin-α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3-dependent manner. Int. J. Cancer 2019, 145, 1358–1370.
  132. Gilazieva, Z.; Ponomarev, A.; Rutland, C.; Rizvanov, A.; Solovyeva, V. Promising applications of tumor spheroids and organoids for personalized medicine. Cancers 2020, 12, 2727.
  133. Ehsan, S.M.; Welch-Reardon, K.M.; Waterman, M.L.; Hughes, C.C.W.; George, S.C. A three-dimensional in vitro model of tumor cell intravasation. Integr. Biol. 2014, 6, 603–610.
  134. Buchanan, C.F.; Verbridge, S.S.; Vlachos, P.P.; Rylander, M.N. Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model. Cell Adhes. Migr. 2014, 8, 517–524.
  135. Cauli, E.; Polidoro, M.A.; Marzorati, S.; Bernardi, C.; Rasponi, M.; Lleo, A. Cancer-on-chip: A 3D model for the study of the tumor microenvironment. J. Biol. Eng. 2023, 17, 53.
  136. Clarke, R. Introduction: Cancer Systems and Integrative Biology; Humana: New York, NY, USA, 2023; Volume 2660.
  137. Tuomainen, K.; Al-Samadi, A.; Potdar, S.; Turunen, L.; Turunen, M.; Karhemo, P.-R.; Bergman, P.; Risteli, M.; Åström, P.; Tiikkaja, R.; et al. Human tumor–derived matrix improves the predictability of head and neck cancer drug testing. Cancers 2020, 12, 92.
  138. Naakka, E.; Wahbi, W.; Tiikkaja, R.; Juurikka, K.; Sandvik, T.; Koivunen, P.; Autio, T.; Tikanto, J.; Väisänen, J.; Tuominen, H.; et al. Novel human lymph node-derived matrix supports the adhesion of metastatic oral carcinoma cells. BMC Cancer 2023, 23, 750.
  139. Drost, J.; Clevers, H. Organoids in cancer research. Nat. Rev. Cancer 2018, 18, 407–418.
  140. Pillai, S.; Kwan, J.C.; Yaziji, F.; Yu, H.; Tran, S.D. Mapping the Potential of Microfluidics in Early Diagnosis and Personalized Treatment of Head and Neck Cancers. Cancers 2023, 15, 3894.
  141. Cheah, R.; Srivastava, R.; Stafford, N.D.; Beavis, A.W.; Green, V.; Greenman, J. Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy. Int. J. Oncol. 2017, 51, 1227–1238.
  142. Sawant, S.; Dongre, H.; Singh, A.K.; Joshi, S.; Costea, D.E.; Mahadik, S.; Ahire, C.; Makani, V.; Dange, P.; Sharma, S.; et al. Establishment of 3D co-culture models from different stages of human tongue tumorigenesis: Utility in understanding neoplastic progression. PLoS ONE 2016, 11, e0160615.
  143. Establishment of Squamous Cell Organoids of the Head and Neck to Assess Their Response to Innovative Therapies (ORGAVADS); ClinicalTrials.gov Identifier: NCT04261192. Available online: https://clinicaltrials.gov/study/NCT04261192 (accessed on 1 October 2023).
  144. Perréard, M.; Florent, R.; Divoux, J.; Grellard, J.-M.; Lequesne, J.; Briand, M.; Clarisse, B.; Rousseau, N.; Lebreton, E.; Dubois, B.; et al. ORGAVADS: Establishment of tumor organoids from head and neck squamous cell carcinoma to assess their response to innovative therapies. BMC Cancer 2023, 23, 223.
  145. Selecting Chemotherapy with High-Throughput Drug Screen Assay Using Patient Derived Organoids in Patients with Refractory Solid Tumours (SCORE); ClinicalTrials.gov Identifier: NCT04279509. Available online: https://clinicaltrials.gov/study/NCT04279509 (accessed on 1 October 2023).
  146. SOTO: Treatment Sensitivity of Organoids to Predict Treatment Outcome; ClinicalTrials.gov Identifier: NCT05400239. Available online: https://classic.clinicaltrials.gov/ct2/history/NCT05400239?V_2=View (accessed on 1 October 2023).
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