TY  - JOUR
AU  - Peng, Tianping
AU  - Ma, Xiujian
AU  - Hua, Wei
AU  - Wang, Changwen
AU  - Chu, Youjun
AU  - Sun, Meng
AU  - Fermi, Valentina
AU  - Hamelmann, Stefan
AU  - Lindner, Katharina
AU  - Shao, Chunxuan
AU  - Zaman, Julia
AU  - Tian, Weili
AU  - Zhuo, Yue
AU  - Harim, Yassin
AU  - Stöffler, Nadja
AU  - Hammann, Linda
AU  - Xiao, Qungen
AU  - Jin, Xiaoliang
AU  - Warta, Rolf
AU  - Lotsch, Catharina
AU  - Zhuang, Xuran
AU  - Feng, Yuan
AU  - Fu, Minjie
AU  - Zhang, Xin
AU  - Zhang, Jinsen
AU  - Xu, Hao
AU  - Qiu, Fufang
AU  - Xie, Liqian
AU  - Zhang, Yi
AU  - Zhu, Wei
AU  - Du, Zunguo
AU  - Salgueiro, Lorena
AU  - Schneider, Mark
AU  - Eichhorn, Florian
AU  - Lefevre, Arthur
AU  - Pusch, Stefan
AU  - Grinevich, Valery
AU  - Ratliff, Miriam
AU  - Loges, Sonja
AU  - Bunse, Lukas
AU  - Sahm, Felix
AU  - Xiang, Yangfei
AU  - Unterberg, Andreas
AU  - von Deimling, Andreas
AU  - Platten, Michael
AU  - Herold-Mende, Christel
AU  - Wu, Yonghe
AU  - Liu, Haikun
AU  - Mao, Ying
TI  - Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy.
JO  - Cell stem cell
VL  - 32
IS  - 4
SN  - 1934-5909
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DKFZ-2025-00346
SP  - 652-669.e11
PY  - 2025
N1  - DKFZ-ZMBH Alliance / #EA:A240# / HI-TRON / 2025 Apr 3;32(4):652-669.e11
AB  - 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.
KW  - brain metastasis (Other)
KW  - glioblastoma (Other)
KW  - patient tumor organoid (Other)
KW  - predictive patient model (Other)
KW  - temozolomide (Other)
KW  - tumor heterogeneity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39938519
DO  - DOI:10.1016/j.stem.2025.01.002
UR  - https://inrepo02.dkfz.de/record/298907
ER  -