头颈部恶性肿瘤研究模型的演化  

Evolution of research models for malignant head and neck tumors

作　　者：王安训[1] 周万航 曹琮沅 WANG Anxun;ZHOU Wanhang;CAO Congyuan(Department of Oral and Maxillofacial Surgery,the First Affiliated Hospital,Sun Yat-Sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院口腔颌面外科,广东广州510055

出　　处：《口腔疾病防治》2024年第9期653-663,共11页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金面上项目(82372868,82173041)。

摘　　要：恶性肿瘤发生发展的机制探索以及抗癌药物治疗疗效的评估均有赖于各种体内与体外研究模型的建立。近几十年间,随着生物医学技术的快速发展,恶性肿瘤的体内外研究模型也发生了巨大的变化。基因检测技术从单基因到多基因的进展促进了生物信息学飞速发展和恶性肿瘤概念的转变;体外细胞研究模型从单层的二维培养、原代培养向立体的三维构型发展,从而更好地重现肿瘤组织的细胞间交互作用与功能;体内动物研究模型由传统的致癌物诱导、细胞或组织形成移植瘤逐渐演变为基因编辑的动物模型或人源性肿瘤异种移植模型,从而可以针对性地研究相关基因在肿瘤发生发展中的作用;传统的临床研究也从简单的临床回顾性研究更多地向前瞻性研究转变,Ⅰ期/Ⅱ期/Ⅲ期临床研究,研究者发起的临床研究以及真实世界临床研究,这些研究为临床研究增添了活力。目前恶性肿瘤研究模型存在的主要不足包括模型的单一性、对肿瘤微环境的模拟不足、动物肿瘤模型与人类肿瘤差异性,以及缺乏对个性化医疗的考量。未来仍需要进一步研发和优化研究模型,并更有效地将不同模型整合起来,形成一个优化的整体实验模型系统。本文将系统回顾恶性肿瘤研究模型的演化并对相关模型进行阐述,为科研工作者进行恶性肿瘤的研究提供合理的研究模型。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 in vivo and in vitro.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,in vitro 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,in vivo 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 phaseⅠ/Ⅱ/Ⅲclinical trials,investigatorinitiated clinical trials,and real-world clinical trials.The major shortcom-ings 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.

关 键 词：恶性肿瘤 研究模型 3D培养技术 肿瘤类器官培养 动物模型 人源肿瘤细胞系异种移植瘤 人源性肿瘤异种移植模型 基因检测 生物信息学 数字肿瘤学 智能肿瘤学 

分 类 号：R78[医药卫生—口腔医学]