Abstract:
Head and neck squamous cell carcinoma (HNSCC) outcomes remain stagnant, in part due to a poor understanding of HNSCC biology. The importance of tumor heterogeneity as an independent predictor of outcomes and treatment failure in HNSCC has recently come to light. With this understanding, 3D culture systems, including patient derived organoids (PDO) and organotypic culture (OTC), that capture this heterogeneity may allow for modeling and manipulation of critical subpopulations, such as p-EMT, as well as interactions between cancer cells and immune and stromal cells in the microenvironment. Here, we review work that has been done using PDO and OTC models of HNSCC, which demonstrates that these 3D culture models capture in vivo tumor heterogeneity and can be used to model tumor biology and treatment response in a way that faithfully recapitulates in vivo characteristics. As such, in vitro 3D culture models represent an important bridge between 2D monolayer culture and in vivo models such as patient derived xenografts.
摘要:
头颈部鳞状细胞癌(HNSCC)结果仍然停滞不前,部分原因是对HNSCC生物学的理解不足。肿瘤异质性作为HNSCC结果和治疗失败的独立预测因子的重要性最近逐渐显现出来。有了这个认识,3D文化系统,包括患者来源的类器官(PDO)和器官型培养(OTC),捕获这种异质性可以允许对关键亚群进行建模和操纵,比如p-EMT,以及微环境中癌细胞与免疫细胞和基质细胞之间的相互作用。这里,我们回顾了使用HNSCC的PDO和OTC模型所做的工作,这表明这些3D培养模型捕获了体内肿瘤异质性,并可用于以忠实地概括体内特征的方式对肿瘤生物学和治疗反应进行建模。因此,体外3D培养模型代表了2D单层培养和体内模型(例如患者来源的异种移植物)之间的重要桥梁。