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弥合差距:患者来源的肺癌类器官如何改变个性化医疗。

Bridging the gap: how patient-derived lung cancer organoids are transforming personalized medicine.

作者信息

Liu Chaoxing, Shi Chao, Wang Siya, Qi Rong, Gu Weiguo, Yu Feng, Zhang Guohua, Qiu Feng

机构信息

Department of Oncology, Gaoxin Branch of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Nanchang Key Laboratory of Tumor Gene Diagnosis and Innovative Treatment Research, Gaoxin Branch of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

Front Cell Dev Biol. 2025 Apr 15;13:1554268. doi: 10.3389/fcell.2025.1554268. eCollection 2025.

Abstract

Lung cancer is a major malignancy that poses a significant threat to human health, with its complex pathogenesis and molecular characteristics presenting substantial challenges for treatment. Traditional two-dimensional cell cultures and animal models are limited in their ability to accurately replicate the characteristics of different lung cancer patients, thereby hindering research on disease mechanisms and treatment strategies. The development of organoid technology has enabled the growth of patient-derived tumor cells in three-dimensional cultures, which can stably preserve the tumor's tissue morphology, genomic features, and drug response. There have been significant advancements in the field of patient-derived lung cancer organoids (PDLCOs), challenges remain in the reproducibility and standardization of PDLCOs models due to variations in specimen sources, subsequent processing techniques, culture medium formulations, and Matrigel batches. This review summarizes the cultivation and validation processes of PDLCOs and explores their clinical applications in personalized treatment, drug screening after resistance, PDLCOs biobanks construction, and drug development. Additionally, the integration of PDLCOs with cutting-edge technologies in various fields, such as tumor assembloid techniques, artificial intelligence, organoid-on-a-chip, 3D bioprinting, gene editing, and single-cell RNA sequencing, has greatly expanded their clinical potential. This review, incorporating the latest research developments in PDLCOs, provides an overview of their cultivation, clinical applications, and interdisciplinary integration, while also addressing the prospects and challenges of PDLCOs in precision medicine for lung cancer.

摘要

肺癌是一种对人类健康构成重大威胁的主要恶性肿瘤,其复杂的发病机制和分子特征给治疗带来了巨大挑战。传统的二维细胞培养和动物模型在准确复制不同肺癌患者特征方面能力有限,从而阻碍了对疾病机制和治疗策略的研究。类器官技术的发展使患者来源的肿瘤细胞能够在三维培养中生长,可稳定保留肿瘤的组织形态、基因组特征和药物反应。患者来源的肺癌类器官(PDLCOs)领域已取得重大进展,但由于标本来源、后续处理技术、培养基配方和基质胶批次的差异,PDLCOs模型的可重复性和标准化仍存在挑战。本文综述了PDLCOs的培养和验证过程,并探讨了它们在个性化治疗、耐药后药物筛选、PDLCOs生物样本库建设和药物研发中的临床应用。此外,PDLCOs与肿瘤类组装体技术、人工智能、芯片上类器官、3D生物打印、基因编辑和单细胞RNA测序等各个领域的前沿技术相结合,极大地扩展了它们的临床潜力。本文结合了PDLCOs的最新研究进展,概述了它们的培养、临床应用和跨学科整合,同时也探讨了PDLCOs在肺癌精准医学中的前景和挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4498/12037501/d96e8ea892e5/fcell-13-1554268-g001.jpg

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