Lung cancer is the leading cause of global cancer-related mortality resulting in ∼ 1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based drug screening studies. Lung cancer PDOs were successfully established from fresh or bio-banked sections and/or biopsies, pleural effusions and PDX mouse models. PDOs were subject to drug screening with chemotherapy, targeted therapy and/or immunotherapy. PDOs consistently recapitulated the genomic alterations and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remain, PDOs showed great promise in the screening of novel therapy drugs. With the technical advances of high throughput, tumor-on-chip, and combined microenvironment, the drug screening process using PDOs will enhance precision care of lung cancer patients.

中文翻译：

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对患者肺类器官进行体外药物测试，以预测个性化医疗的治疗反应

肺癌是全球癌症相关死亡的主要原因，每年导致约 180 万人死亡。全身、分子靶向和免疫疗法显着改善了患者的生存结果。然而，耐药性通常会出现，迫切需要新的治疗筛选和个性化医疗。 3D 患者来源的类器官 (PDO) 模型已成为比 2D 细胞培养和患者来源的异种移植 (PDX) 模型更有效和高效的药物筛选替代方案。在这篇综述中，我们对基于 PDO 的肺癌药物筛选研究进行了广泛的检索。肺癌 PDO 是从新鲜或生物库切片和/或活检、胸腔积液和 PDX 小鼠模型成功建立的。 PDO 接受化疗、靶向治疗和/或免疫治疗的药物筛选。 PDO 一致地概括了原发性肿瘤的基因组改变和药物敏感性。尽管之前的研究样本量有限并且仍然存在一些技术挑战，但 PDO 在筛选新型治疗药物方面显示出巨大的前景。随着高通量、肿瘤芯片和组合微环境的技术进步，使用PDO的药物筛选过程将增强肺癌患者的精准护理。