Three current approaches to preclinical oral squamous cell carcinoma research: a practical, stepwise framework integrating cell lines, organoids, and animal models.

Oral squamous cell carcinoma (OSCC) continues to be associated with a poor prognosis despite recent advances in surgical and adjuvant treatment. Although a variety of experimental models are available, no widely accepted or practical framework has combined cell lines, patient-derived organoids, and in vivo transplantation models in translational OSCC research. This review summarizes the main preclinical models used in OSCC research and discusses how they can be used together in a stepwise manner for drug development. A narrative review of the literature was conducted focusing on OSCC research cell lines, organoids, and transplantation smodels, as well as studies that have applied artificial intelligence (AI) and multi-omics analyses. Cell lines are useful for reproducible mechanistic studies and initial drug screening. Organoids better preserve tumour heterogeneity and allow patient-specific testing. Orthotopic transplantation models reproduce local invasion, metastatic spread, and interactions with the tumour microenvironment. When data from these platforms are analysed together and, where appropriate, supported by AI-based imaging and molecular profiling, their translational relevance may be enhanced. Combining cell lines, organoids, and in vivo models in a planned, stepwise approach provides a practical framework for OSCC research. This approach may help bridge the gap between experimental studies and clinical practice, particularly in oral and maxillofacial surgery.