人体类器官技术的发展及其在肿瘤精准医学中的应用

吴梦叶1,2 , 付 静2,* , 王红阳2,*
1安徽理工大学医学院,淮南 232001 2海军军医大学第三附属医院/国家肝癌科学中心国际合作生物信 号转导研究中心,上海 200438

摘 要:

人体类器官是一种基于干细胞自组织能力建立的新型三维生物模型,可在体外重建人体组织器官的部分结构特征和核心功能,为疾病机制解析、新药研发、药物筛选及个体化治疗等提供了新的技术平台。恶性肿瘤是严重威胁人类生命健康的重大疾病,其高度异质性、动态演进性与治疗适应性等,使早期诊断、疾病分型、个体化治疗、疗效预测和耐药管理面临严峻挑战。传统二维细胞培养和动物模型虽在肿瘤机制研究及药物研发中发挥一定的基础性作用,但仍存在组织结构和微环境模拟不足、物种间生物学差异显著、临床转化效率有限等局限。构建更贴近人体生理与病理特征,能够动态、全貌反映患者个体差异的新型研究模型,已成为推动肿瘤精准医学发展的重要方向和范式变革。本文系统综述人体类器官技术的发展历程、技术特点、攻坚难点及其在肿瘤精准诊疗中的应用进展,并结合本团队在肝胆肿瘤类器官研究领域的实践,重点探讨其在规范化建库、个体化用药和晚期患者动态疗效评估中的应用价值。在此基础上,本文进一步剖析当前类器官技术在标准化、规模化及临床转化方面面临的挑战,展望其与微流控芯片、人工智能等技术融合的智能化发展趋势。类器官技术的持续完善有望打通多学科基础研究与临床转化链条,为肿瘤精准分型、个体化干预及全周期疾病管理提供新的技术支撑。

通讯作者:付 静 , Email:fujing-724@163.com 王红阳 , Email:hywangk@vip.sina.com

Development of human organoid technology and its applications in precision oncology
WU Meng-Ye1,2 , FU Jing2,* , WANG Hong-Yang2,*
1School of Medicine, Anhui University of Science & Technology, Huainan 232001, China 2International Cooperation Laboratory on Signal Transduction, National Center for Liver Cancer, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China

Abstract:

Human organoids are emerging three-dimensional (3D) biological models established based on the self-organizing capacity of stem cells. By partially recapitulating the structural features and key physiological functions of human tissues and organs in vitro, organoids provide a powerful technological platform for elucidating disease mechanisms, accelerating drug novel drug development, enabling high-throughput drug screening, and advancing personalized medicine. Malignant tumors  represent a major global health challenge. Their profound intratumoral heterogeneity, dynamic evolutionary trajectories, and adaptive responses to therapeutic pressure pose substantial challenges for early diagnosis, molecular classification,  individualized treatment strategies, prediction of therapeutic responses, and management of acquired drug resistance.  Although conventional two-dimensional (2D) cell culture systems and animal models have served as essential tools for cancer  biology research and preclinical drug development, they remain limited by inadequate recapitulation of tissue architecture and  tumor microenvironmental complexity, significant interspecies biological discrepancies, and limited clinical translatability.  Therefore, the development of innovative research models that faithfully reproduce human physiological and pathological  states while preserving patient-specific characteristics has become a critical strategy for advancing precision oncology. This review provides a comprehensive overview of the evolution, technological features, emerging applications and current  challenges of human organoid technology in precision cancer diagnosis and treatment. Building upon our team’s extensive  experience in hepatobiliary tumor organoid research, we highlight the translational potential of organoids in standardized biobanking, personalized drug selection, and longitudinal monitoring of therapeutic responses in patients with advanced  malignancies. Furthermore, we discuss the major obstacles hindering the widespread clinical application of organoid  technology, particularly those related to standardization, scalability, and clinical implementation, and explore future  perspectives involving the integration of organoid platforms with microfluidic systems, artificial intelligence, and other advanced technologies. Continued advances in organoid technology are expected to bridge the gap between basic biomedical research and clinical practice, providing innovative approaches for precision tumor stratification, personalized therapeutic intervention, and comprehensive cancer management across the disease continuum.

Communication Author:FU Jing , Email:fujing-724@163.com WANG Hong-Yang , Email:hywangk@vip.sina.com

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