肿瘤类器官:发展、应用及挑战

Organoid in cancer research:Progress,applications and challenges

现有肿瘤模型难以完美模拟体内肿瘤真实状态,导致众多研究折戟于临床试验.类器官作为一种3D细胞结构,可再现体内肿瘤的生理活动,是迄今为止最接近体内真实状态的人类癌症模型.类器官可从病人的正常及恶性组织中建立,与目前主流的2D细胞培养、转基因鼠、人源肿瘤异种移植模型(Patient-derived tumor xenograft,PDTX)等肿瘤模型相比,其可用于研究感染或基因突变导致的癌症发生,并且在临床药物开发及指导个体化治疗方面具有独特优势.尽管类器官仍不能准确模拟免疫系统,但一些研究中已经报道了类器官和淋巴细胞的共同培养为该技术在免疫疗法中的进一步应用带来了希望.此外,基于微流控技术构建的类器官集成系统也为研究肿瘤微环境中的相互作用提供了可靠模型.本文总结了近年来类器官技术在癌症领域中的相关研究及挑战,旨在阐明肿瘤类器官在癌症研究中的价值,为后续研究提供方向.

Current tumor models do not perfectly simulate the natural state of tumors in vivo,which has led to many studies faltering in clinical trials.As a 3Dcellular structure,an organism can reproduce the physiological activities of tumors in vivo and is the closest human cancer model to the natural state in vivo so far.The organoid can be established from both normal and malignant tissues of patients,and can be used to study cancer development caused by infection or genetic mutation,and has unique advantages in clinical drug development and guiding individualized treatment compared with the mainstream 2Dcell culture,transgenic mouse,and human-derived tumor xenograft(PDTX)tumor models.It has unique advantages in clinical drug development and guiding individualized therapy.Although organoids remain unable to mimic the immune system accurately,the co-culture of organoids and lymphocytes has been reported in several studies to provide hope for further applications of this technology in immunotherapy.In addition,the construction of integrated organoid systems based on microfluidics also provides a reliable model for studying interactions in the tumor microenvironment.This paper summarizes the relevant studies and challenges of organoid technology in cancer in recent years,aiming to clarify the value of organoids in cancer research and provide directions for future research.