类器官在肿瘤转化医学中的应用和进展

随着精准医学概念的提出,肿瘤作为一类高度异质性的疾病,其个体化治疗已成为精准医学的一个关键领域也受到更多关注。近期提出的类器官模型为肿瘤的基础研究和个体化治疗带来了新突破。类器官指从干细胞或器官祖细胞来源,以类似体内细胞分化的方式组织成的器官特异性的细胞集合。肿瘤类器官指利用原代恶性细胞经过体外3D培养构建的恶性细胞团,在体外培养条件下可持续增殖,一定程度上保留了原代肿瘤的病理学形态特征、基因组与转录组特征、药物敏感性及恶性细胞间异质性,为体外肿瘤研究提供了新方法,尤其在预测患者药物敏感性、药物高通量筛选等方面有巨大潜力,为肿瘤个体化治疗作出了贡献。但该模型仍存在不足,如无法重现体内肿瘤微环境等,使其在临床等方面的应用受限。目前将肿瘤类器官与其他肿瘤成分共培养、与微流控设备和生物打印技术等联合应用将有望弥补其缺陷、突破肿瘤治疗领域的瓶颈。本文将常用肿瘤研究模型的特点进行对比,总结部分肿瘤类器官的培养方法,并描述了肿瘤类器官的临床相关应用,最后对其与其他技术联合应用进行了叙述,并对未来肿瘤类器官的发展方向予以展望。

Application and progress of organoids in tumor translational medicine

With the introduction of precision medicine, the individualized treatment of cancer has raised increasing interest in the field. Recently, the utilization of organoids as a powerful tool for precision medicine has achieved great breakthroughs for basic research and potential clinical usage. Organoids usually derived from stem/progenitor cells are organ-specific multi-cell clusters organized in a manner like the cell differentiation patterns of their original in vivo counterpart. While keeping the basic pathological/genetic/biological phenotypes of their parental primary cells/tissues, tumor organoids still have a certain potential for proliferative immortalization, which makes organoid-based research/clinical models hopeful tools for precision medicine, especially in predicting drug sensitivity for clinical patients or conducting high-throughput screening of new compounds/drugs for pharmaceutical development. However, obstacles still exist to the clinical application of organoid-based tools, such as the lack of in vivo tumor microenvironment. Currently, with the development of co-culture, microfluidic and bioprinting techniques, breakthroughs have been made for the practical clinical/industrial utilization of organoids. In the current review, we compared the characteristics of common ex vivo tumor models with organoid-based models, summarized the protocols for tumor organoid culturing, reviewed the clinical/industrial application of tumor organoids, and finally look forward to the new outlooks of tumor organoid-based tools in the future.