复旦大学毛颖团队研究发现，个体化患者肿瘤类器官忠实地保存人类脑肿瘤生态系统并预测患者对治疗的反应。这一研究成果发表在2025年2月11日出版的国际学术期刊《细胞—干细胞》上。

研究团队开发了一种快速，高效，复杂的培养系统（IPTO，个体化患者肿瘤类器官），准确地概括了人类脑肿瘤的细胞和分子病理。患者来源的肿瘤外植体在诱导多能干细胞（iPSC）来源的脑类器官中培养，它们能够培养广泛的中枢神经系统（CNS）人类肿瘤，包括成人、儿童和转移性脑癌。组织病理学、基因组学、表观基因组学和单细胞RNA测序（scRNA-seq）分析表明，IPTO模型再现了原始肿瘤的细胞异质性和分子特征。

至关重要的是，该研究团队证明了IPTO模型在前瞻性患者队列中预测了患者特异性药物反应，包括耐药机制。总的来说，IPTO模型代表了人类癌症临床前建模的重大突破，为个性化癌症治疗提供了一条途径。

据介绍，肿瘤类器官是癌症研究的重要工具，但目前的模型存在缺陷，限制了它们在预测治疗反应方面的应用。

附：英文原文

Title: Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy

Author: Tianping Peng, Xiujian Ma, Wei Hua, Changwen Wang, Youjun Chu, Meng Sun, Valentina Fermi, Stefan Hamelmann, Katharina Lindner, Chunxuan Shao, Julia Zaman, Weili Tian, Yue Zhuo, Yassin Harim, Nadja Stffler, Linda Hammann, Qungen Xiao, Xiaoliang Jin, Rolf Warta, Catharina Lotsch, Xuran Zhuang, Yuan Feng, Minjie Fu, Xin Zhang, Jinsen Zhang, Hao Xu, Fufang Qiu, Liqian Xie, Yi Zhang, Wei Zhu, Zunguo Du, Lorena Salgueiro, Mark Schneider, Florian Eichhorn, Arthur Lefevre, Stefan Pusch, Valery Grinevich, Miriam Ratliff, Sonja Loges, Lukas Bunse, Felix Sahm, Yangfei Xiang, Andreas Unterberg, Andreas von Deimling, Michael Platten, Christel Herold-Mende, Yonghe Wu, Hai-Kun Liu, Ying Mao

Issue&Volume: 2025-02-11

Abstract: Tumor organoids are important tools for cancer research, but current models have drawbacks that limit their applications for predicting response to therapy. Here, we developed a fast, efficient, and complex culture system (IPTO, individualized patient tumor organoid) that accurately recapitulates the cellular and molecular pathology of human brain tumors. Patient-derived tumor explants were cultured in induced pluripotent stem cell (iPSC)-derived cerebral organoids, thus enabling culture of a wide range of human tumors in the central nervous system (CNS), including adult, pediatric, and metastatic brain cancers. Histopathological, genomic, epigenomic, and single-cell RNA sequencing (scRNA-seq) analyses demonstrated that the IPTO model recapitulates cellular heterogeneity and molecular features of original tumors. Crucially, we showed that the IPTO model predicts patient-specific drug responses, including resistance mechanisms, in a prospective patient cohort. Collectively, the IPTO model represents a major breakthrough in preclinical modeling of human cancers, which provides a path toward personalized cancer therapy.

DOI: 10.1016/j.stem.2025.01.002

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00002-5