Evolution of research models for malignant head and neck tumors

Exploration of the underlying mechanisms of tumor occurrence and development, as well as evaluation of the efficacy of anticancer drug treatments, relies on various research models both <i>in vivo</i> and <i>in vitro</i>. Over the past few decades, with the rapid advancement of biomedical technology, significant achievements have been made in this field. Gene detection technology has progressed from a single-gene perspective to multi-gene approaches, resulting in rapid development of bioinformatics and transformation of the conceptual understanding of malignant tumors. Moreover, <i>in vitro</i> cell research models have evolved from monolayer two-dimensional and primary cultures to three-dimensional configurations, which better imitate the cellular interactions and functions within tumor tissues. Furthermore, <i>in vivo</i> animal research models have transitioned from traditional carcinogen induction and cell or tissue xenografts to genetically engineered animal models or xenograft models, enabling targeted investigation into the roles of relevant genes in the occurrence and development of tumors. Clinical research has shifted from simple retrospective to prospective studies, including phase Ⅰ/Ⅱ/Ⅲ clinical trials, investigator-initiated clinical trials, and real-world clinical trials. The major shortcomings of current malignant tumor research models include their singularity, insufficient simulation of the tumor microenvironment, disparities between animal models and human tumors, and the lack of consideration for personalized medicine. Further research and optimization of the models are still needed in the future, along with more effective integration of different models to form an optimized comprehensive experimental model system. This review systematically examines and comprehensively overviews the evolution of malignant tumor research models with the aim of providing more references to researchers engaged in oncology research.