Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Semin Liver Dis. 2021 Jan;41(1):19-27. doi: 10.1055/s-0040-1719176. Epub 2021 Feb 9.
Liver cancer is the second most lethal malignancy worldwide. Cell lines and murine models are the most common tools for modeling human liver carcinogenesis. Most recently, organoids with a three-dimensional structure derived from primary tissues or cells have been applied to liver cancer research. Organoids can be generated from induced pluripotent stem cells, embryonic or adult, healthy or diseased tissues. In particular, liver organoids have been widely employed in mechanistic studies aimed at delineating the molecular pathways responsible for hepatocarcinogenesis. The introduction of clustered regularly interspaced palindromic repeats (CRISPR)-associated protein 9 (Cas9) and microengineered miniorganoid technologies into liver organoids for cancer study has significantly accelerated these investigations. Translational advances have been made by utilizing liver tumor organoids for anticancer drug screening, biobanking, omics profiling, and biomarker discovery. This review summarizes the latest advances and the remaining challenges in the use of organoid models for the study of liver cancer.
肝癌是全球第二大致命恶性肿瘤。细胞系和小鼠模型是模拟人类肝癌发生的最常用工具。最近，源自原发性组织或细胞的具有三维结构的类器官已被应用于肝癌研究。类器官可由诱导多能干细胞、胚胎或成人、健康或患病组织生成。特别是，肝类器官已广泛应用于旨在阐明导致肝癌发生的分子途径的机制研究。将成簇规律间隔短回文重复序列（CRISPR）相关蛋白 9（Cas9）和微型工程类器官技术引入肝类器官进行癌症研究，极大地加速了这些研究。通过利用肝肿瘤类器官进行抗癌药物筛选、生物库建立、组学分析和生物标志物发现，已经取得了转化进展。本综述总结了利用类器官模型研究肝癌的最新进展和尚存挑战。
