拟人化模型指导精准治疗的现状与挑战

The status and challenges of anthropomorphic models in precision medicine

临床前模型在癌症的病因、发病机制和治疗评估中发挥着举足轻重的作用。迄今为止,临床前小鼠模型是最常用且可靠的抗肿瘤药物疗效和安全评价平台,其伴随着癌症研究的革新而不断发展。近年来,相较于细胞系来源的小鼠模型和基因工程小鼠模型等传统研究模型,利用患者来源的肿瘤组织或细胞建立的拟人化模型,因其能够最大限度保留患者肿瘤的组织病理学、分子遗传学特征以及对药物的反应,逐渐成为临床前研究中更合适的"患者替身"。本文简述了拟人化模型的发展历程,总结了其在筛选药物新靶点、评估药物疗效和预测标志物、探索耐药机制和逆转策略、开展同步临床试验以及指导个体化治疗等方面的优势,并对该模型在建立和应用中存在的问题进行进一步的分析和展望。

Animal models play a pivotal role in the etiology,pathogenesis and treatment evaluation of cancer.So far,preclinical mouse models are the most commonly used and reliable platform for evaluating efficacy and safety of antitumor drug,which has been constantly developed with the innovation of cancer research.Recently,compared with traditional research models such as cell line-derived mouse models and genetically engineered mouse models,anthropomorphic animal models become the more suitable "avatar" in preclinical research.The anthropomorphic models are established using patient-derived tumor tissues or cells,which can preserve the pathology,genetics,and drug response of patients to the greatest extent.This review briefly describes the development of anthropomorphic models.In addition,we summarize the application of anthropomorphic models in screening novel targets,evaluation drug efficacy and biomarkers,exploring resistance mechanisms and reversal strategies,conducting co-clinical trials,and guiding individualized therapy.At last,the advantages and challenges during the establishment and application of anthropomorphic models are further analyzed and prospected.