Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Department of Medicine, Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX, USA.
Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Lung Cancer. 2024 Apr;190:107533. doi: 10.1016/j.lungcan.2024.107533. Epub 2024 Mar 14.
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 ex vivo 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 ex vivo 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 ex vivo 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.
肺癌是导致全球癌症相关死亡的主要原因，每年导致约 180 万人死亡。系统治疗、分子靶向治疗和免疫治疗为患者的生存结果提供了显著改善。然而，耐药性通常会出现，因此迫切需要新的治疗方法筛选和个性化医疗。与 2D 细胞培养和患者来源的异种移植 (PDX) 模型相比，3D 患者来源的类器官 (PDO) 模型作为一种更有效和高效的体外药物筛选方法已经出现。在这篇综述中，我们对基于肺癌 PDO 的体外药物筛选研究进行了广泛的搜索。从新鲜或生物银行切片和/或活检、胸腔积液和 PDX 小鼠模型中成功建立了肺癌 PDO。PDO 接受了化疗、靶向治疗和/或免疫治疗的体外药物筛选。PDO 一致地重现了原发性肿瘤的基因组改变和药物敏感性。尽管以前研究的样本量有限，并且存在一些技术挑战，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、肿瘤芯片和联合微环境技术的进步，使用 PDO 进行药物筛选将增强对肺癌患者的精准护理。
