Three-Dimensional Organoids in Oral Cancer Research: A Paradigm Shift in Oncology
DOI:
https://doi.org/10.48165/ajm.2026.9.01.32Keywords:
Organoids, Oral cancer, OSCC, 3D culture, Personalized medicineAbstract
Oral cancer, predominantly oral squamous cell carcinoma (OSCC), remains a major global health burden with high morbidity and mortality rates. Traditional two-dimensional (2D) cell cultures and animal models often fail to accurately replicate tumor heterogeneity and the complex tumor microenvironment. Organoids, three-dimensional (3D) in vitro culture systems derived from stem cells or tumor tissues, have emerged as a revolutionary tool in cancer research. Oral cancer organoids closely mimic the histological architecture, genetic profile, and functional characteristics of the original tumor. This review discusses the concept, development, methodologies, and applications of organoids in oral cancer research, highlighting their role in disease modeling, drug screening, and personalized medicine. Additionally, limitations, challenges, and future prospects are addressed.
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Tan Y, Wang Z, Xu M, Li B, Huang Z, Qin S, Nice EC, Tang J, Huang C. Oral squamous cell carcinomas: state of the field and emerging directions. Int J Oral Sci. 2023;15(1):44. doi:10.1038/s41368-023-00227-1.
Bagan J, Sarrion G, Jimenez Y. Oral cancer: clinical features. Oral Oncol. 2010;46(6):414–417. doi:10.1016/j.oraloncology.2010.03.017.
Esposito A, Ferraresi A, Vallino L, Garavaglia B, Dhanasekaran DN, Isidoro C. Three-dimensional in vitro cell cultures as a feasible and promising alternative to two-dimensional and animal models in cancer research. Int J Biol Sci. 2024;20(13):5293–5311.
Yang S, Hu H, Kung H, Zou R, Dai Y, Hu Y, Wang T, Lv T, Yu J, Li F. Organoids: the current status and biomedical applications. MedComm (2020). 2023;4(3):e274. doi:10.1002/mco2.274.
Fan H, Demirci U, Chen P. Emerging organoid models: leaping forward in cancer research. J Hematol Oncol. 2019;12(1):142. doi:10.1186/s13045-019-0812-4.
Wu Y, Li X, Liu H, Yang X, Li R, Zhao H, et al. Organoids in the oral and maxillofacial region: present and future. Int J Oral Sci. 2024;16(1):61. doi:10.1038/s41368-024-00278-5.
Gao X, Wu Y, Liao L, Tian W. Oral organoids: progress and challenges. J Dent Res. 2021;100(5):454–463. doi:10.1177/0022034520977734.
Li FC, Kishen A. 3D organoids for regenerative endodontics. Biomolecules. 2023;13(6):900. doi:10.3390/biom13060900.
Driehuis E, et al. Patient-derived oral mucosa organoids as an in vitro model for methotrexate-induced toxicity in pediatric acute lymphoblastic leukemia. PLoS One. 2020;15(5):e0231588. doi:10.1371/journal.pone.0231588.
Hisha H, Tanaka T, Ueno H. Lingual epithelial stem cells and organoid culture of them. Int J Mol Sci. 2016;17(2):168. doi:10.3390/ijms17020168.
Lee MR, Kang S, Lee J, Kong SY, Kim Y, Lee YS, Shon HW, Kang G, Lee J, Youn SM, Kwack DW, Park JY, Kim SM, Choi W, Lee JH, Shin D, Kwon IJ, Choi SW, Kim YH. Organoid morphology-guided classification for oral cancer reveals prognosis. Cell Rep Med. 2025;6(5):102129. doi:10.1016/j.xcrm.2025.102129.
Wang Y, Sun X, Lu B, Zhang D, Yin Y, Liu S, Chen L, Zhang Z. Current applications, future perspectives and challenges of organoid technology in oral cancer research. Eur J Pharmacol. 2025;993:177368. doi:10.1016/j.ejphar.2025.177368.
Varinelli L, Illescas O, Lorenc EJ, Battistessa D, Di Bella M, Zanutto S, Gariboldi M. Organoids technology in cancer research: from basic applications to advanced ex vivo models. Front Cell Dev Biol. 2025;13:1569337. doi:10.3389/fcell.2025.1569337.
Huang C, Sanaei F, Verdurmen WPR, Yang F, Ji W, Walboomers XF. The application of organs-on-a-chip in dental, oral, and craniofacial research. J Dent Res. 2023;102(4):364–375. doi:10.1177/00220345221143264.
Thalakiriyawa DS, Dissanayaka WL. Advances in regenerative dentistry approaches: an update. Int Dent J. 2024;74(1):25–34. doi:10.1016/j.identj.2023.07.002.
