The First Affiliated Hospital of Shantou University, Shantou University Medical College, Shantou, China.
Department of Urology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China; Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen, China; International Cancer Center of Shenzhen University, Shenzhen, China.
Prog Mol Biol Transl Sci. 2022;189(1):259-326. doi: 10.1016/bs.pmbts.2022.03.004. Epub 2022 Apr 22.
Cancer represents a leading cause of death, despite the rapid progress of cancer research, leading to urgent need for accurate preclinical model to further study of tumor mechanism and accelerate translational applications. Cancer cell lines cannot fully recapitulate tumors of different patients due to the lack of tumor complexity and specification, while the high technical difficulty, long time, and substantial cost of patient-derived xenograft model makes it unable to be used extensively for all types of tumors and large-scale drug screening. Patient-derived organoids can be established rapidly with a high success rate from many tumors, and precisely replicate the key histopathological, genetic, and phenotypic features, as well as therapeutic response of patient tumor. Therefore, they are extensively used in cancer basic research, biobanking, disease modeling and precision medicine. The combinations of cancer organoids with other advanced technologies, such as 3D bio-printing, organ-on-a-chip, and CRISPR-Cas9, contributes to the more complete replication of complex tumor microenvironment and tumorigenesis. In this review, we discuss the various methods of the establishment and the application of patient-derived organoids in diverse tumors as well as the limitations and future prospects of these models. Further advances of tumor organoids are expected to bridge the huge gap between bench and bedside and provide the unprecedented opportunities to advance cancer research.
癌症是主要的死亡原因之一,尽管癌症研究进展迅速,但仍迫切需要准确的临床前模型来进一步研究肿瘤机制并加速转化应用。由于缺乏肿瘤的复杂性和特异性,癌细胞系不能完全重现不同患者的肿瘤,而患者来源的异种移植模型由于技术难度高、时间长和成本高,无法广泛应用于所有类型的肿瘤和大规模药物筛选。患者来源的类器官可以从许多肿瘤中快速建立,成功率高,能够精确复制患者肿瘤的关键组织病理学、遗传和表型特征以及治疗反应。因此,它们广泛应用于癌症基础研究、生物库、疾病建模和精准医学。癌症类器官与其他先进技术(如 3D 生物打印、芯片上器官和 CRISPR-Cas9)的结合有助于更完整地复制复杂的肿瘤微环境和肿瘤发生。在这篇综述中,我们讨论了建立和应用患者来源的类器官在不同肿瘤中的各种方法,以及这些模型的局限性和未来前景。肿瘤类器官的进一步发展有望弥合基础研究和临床之间的巨大差距,为推进癌症研究提供前所未有的机会。