Patient-centered precision oncology strives to deliver individualized cancer care. In lung cancer, preclinical models and technological innovations have become critical in advancing this approach. Preclinical models enable deeper insights into tumor biology and enhance the selection of appropriate systemic therapies across chemotherapy, targeted therapies, immunotherapies, antibody–drug conjugates, and emerging investigational treatments. While traditional human lung cancer cell lines offer a basic framework for cancer research, they often lack the tumor heterogeneity and intricate tumor–stromal interactions necessary to accurately predict patient-specific clinical outcomes. Patient-derived xenografts (PDXs), however, retain the original tumor’s histopathology and genetic features, providing a more reliable model for predicting responses to systemic therapeutics, especially molecularly targeted therapies. For studying immunotherapies and antibody–drug conjugates, humanized PDX mouse models, syngeneic mouse models, and genetically engineered mouse models (GEMMs) are increasingly utilized. Despite their value, these in vivo models are costly, labor-intensive, and time-consuming. Recently, patient-derived lung cancer organoids (LCOs) have emerged as a promising in vitro tool for functional precision oncology studies. These LCOs demonstrate high success rates in growth and maintenance, accurately represent the histology and genomics of the original tumors and exhibit strong correlations with clinical treatment responses. Further supported by advancements in imaging, spatial and single-cell transcriptomics, proteomics, and artificial intelligence, these preclinical models are reshaping the landscape of drug development and functional precision lung cancer research. This integrated approach holds the potential to deliver increasingly accurate, personalized treatment strategies, ultimately enhancing patient outcomes in lung cancer.
以患者为中心的精准肿瘤学致力于提供个体化癌症治疗。在肺癌领域，临床前模型与技术创新已成为推动这一方法发展的关键。临床前模型能够深入揭示肿瘤生物学特性，并优化化疗、靶向治疗、免疫治疗、抗体偶联药物及新兴实验性治疗等系统性疗法的选择。传统的人类肺癌细胞系虽为癌症研究提供了基础框架，但往往缺乏肿瘤异质性及复杂的肿瘤-间质相互作用，难以准确预测患者特异性临床结局。相比之下，患者来源异种移植模型保留了原始肿瘤的组织病理学与遗传特征，为预测系统性治疗（尤其是分子靶向治疗）反应提供了更可靠的模型。在研究免疫疗法和抗体偶联药物时，人源化PDX小鼠模型、同源小鼠模型及基因工程小鼠模型的应用日益广泛。尽管这些体内模型具有重要价值，但其成本高昂、操作繁琐且耗时较长。近年来，患者来源肺癌类器官作为一种有前景的体外工具，在功能性精准肿瘤学研究中崭露头角。这类肺癌类器官在培养与维持方面展现出高成功率，能准确再现原始肿瘤的组织学与基因组特征，并与临床治疗反应呈现显著相关性。在影像学、空间与单细胞转录组学、蛋白质组学及人工智能等技术进步的推动下，这些临床前模型正在重塑药物研发与功能性精准肺癌研究的格局。这种整合性研究方法有望提供日益精准的个体化治疗策略，最终改善肺癌患者的临床结局。
Preclinical Models for Functional Precision Lung Cancer Research
肿瘤(癌症)患者之家