Zhu Xiaobin, Trehan Rajiv, Xie Changqing
Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA.
J Natl Cancer Cent. 2024 Jun 17;4(3):195-202. doi: 10.1016/j.jncc.2024.06.002. eCollection 2024 Sep.
Primary liver cancer is a leading cause of death worldwide. To create advanced treatments for primary liver cancer, studies have utilized models such as 2D cell culture and animal models. Recent developments in cancer organoids have created the possibility for 3D cultures that recapitulates the cancer cell structure and operation as well as the tumor microenvironment (TME) However, before organoids can be directly translated to clinical use, tissue processing and culture medium must be standardized with unified protocols to decrease variability in results. Herein, we present the wide variety of published methodologies used to derive liver cancer organoids from patient tumor tissues. Additionally, we summarize validation methodologies for organoids in terms of marker expression levels with immunohistochemistry as well as the presence of mutations and variants through RNA-sequencing. Primary liver cancer organoids have exciting applications allowing for faster drug testing at a larger scale. Primary liver cancer organoids also assisit in uncovering new mechanisms. Through the coculture of different immune cells and cancer organoids, organoids are now better able to recapitulate the liver cancer TME. In addition, it further aids in the investigation of drug development and drug resistance. Lastly, we posit that the usage of liver cancer organoids in animal models provides researchers a methodology to overcome the current limitations of culture systems.
原发性肝癌是全球主要的死亡原因之一。为了开发原发性肝癌的先进治疗方法，研究使用了二维细胞培养和动物模型等模型。癌症类器官的最新进展为三维培养创造了可能性，这种三维培养能够重现癌细胞结构和运作以及肿瘤微环境（TME）。然而，在类器官能够直接转化为临床应用之前，组织处理和培养基必须通过统一方案进行标准化，以减少结果的变异性。在此，我们展示了用于从患者肿瘤组织中获得肝癌类器官的各种已发表方法。此外，我们从免疫组织化学检测的标志物表达水平以及通过RNA测序检测的突变和变异情况方面总结了类器官的验证方法。原发性肝癌类器官具有令人兴奋的应用，能够在更大规模上更快地进行药物测试。原发性肝癌类器官还有助于揭示新机制。通过不同免疫细胞与癌症类器官的共培养，类器官现在能够更好地重现肝癌TME。此外，它进一步有助于药物开发和耐药性的研究。最后，我们认为在动物模型中使用肝癌类器官为研究人员提供了一种克服当前培养系统局限性的方法。
