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Abstract：
In December 2022 the US Food and Drug Administration (FDA) removed the requirement that drugs in development must undergo animal testing before clinical evaluation, a declaration that now demands the establishment and verification of ex vivo preclinical models that closely represent tumor complexity and that can predict therapeutic response. Fortunately, the emergence of patient-derived organoid (PDOs) culture has enabled the ex vivo mimicking of the pathophysiology of human tumors with the reassembly of tissue-specific features. These features include histopathological variability, molecular expression profiles, genetic and cellular heterogeneity of parental tissue, and furthermore growing evidence suggests the ability to predict patient therapeutic response. Concentrating on the highly lethal and heterogeneous gastrointestinal (GI) tumors, herein we present the state-of-the-art and the current methodology of PDOs. We highlight the potential additions, improvements and testing required to allow the ex vivo of study the tumor microenvironment, as well as offering commentary on the predictive value of clinical response to treatments such as chemotherapy and immunotherapy.
摘要：
2022年12月，美国食品和药物管理局（FDA）取消了开发中的药物在临床评估之前必须经过动物测试的要求。该声明现在要求建立和验证与肿瘤复杂性密切相关并可以预测治疗反应的体外临床前模型。幸运的是,患者来源的类器官(PDO)培养物的出现使得能够通过重组组织特异性特征来体外模拟人类肿瘤的病理生理学.这些特征包括组织病理学变异性，分子表达谱，亲本组织的遗传和细胞异质性，此外，越来越多的证据表明，预测患者治疗反应的能力。专注于高致死性和异质性胃肠道（GI）肿瘤，本文介绍PDO的最新技术和当前方法。我们强调潜在的补充，改进和测试需要允许离体研究肿瘤微环境，以及对化疗和免疫治疗等治疗的临床反应的预测价值提供评论。
