Zhang Meili, Vandana J Jeya, Lacko Lauretta, Chen Shuibing
Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Tri-Institutional PhD Program in Chemical Biology, Weill Cornell Medicine, The Rockefeller University, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Stem Cell Res. 2020 Dec;49:102063. doi: 10.1016/j.scr.2020.102063. Epub 2020 Oct 27.
Conventional cancer cell lines and animal models have been mainstays of cancer research. More recently, human pluripotent stem cells (hPSCs) and hPSC-derived organoid technologies, together with genome engineering approaches, have provided a complementary platform to model cancer progression. Here, we review the application of these technologies in cancer modeling with respect to the cell-of-origin, cancer propagation, and metastasis. We further discuss the benefits and challenges accompanying the use of hPSC models for cancer research and discuss their broad applicability in drug discovery, biomarker identification, decoding molecular mechanisms, and the deconstruction of clonal and intra-tumoral heterogeneity. In summary, hPSC-derived organoids provide powerful models to recapitulate the pathogenic states in cancer and to perform drug discovery.
传统的癌细胞系和动物模型一直是癌症研究的主要支柱。最近，人类多能干细胞（hPSC）和hPSC衍生的类器官技术，以及基因组工程方法，提供了一个补充平台来模拟癌症进展。在这里，我们回顾这些技术在癌症建模中关于细胞起源、癌症增殖和转移方面的应用。我们进一步讨论使用hPSC模型进行癌症研究所带来的益处和挑战，并讨论它们在药物发现、生物标志物鉴定、解读分子机制以及解构克隆和肿瘤内异质性方面的广泛适用性。总之，hPSC衍生的类器官提供了强大的模型来重现癌症中的致病状态并进行药物发现。
