Patient-Derived Upper Tract Urothelial Carcinoma Organoids as a Platform for Drug Screening.
Patient-Derived Upper Tract Urothelial Carcinoma Organoids as a Platform for Drug Screening.
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患者来源的上尿路上皮癌类器官作为药物筛选的平台
DOI：
10.1002/advs.202103999
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Li Z;Xu H;Gong Y;Chen W;Zhan Y;Yu L;Sun Y;Li A;He S;Guan B;Wu Y;Xiong G;Fang D;He Y;Tang Q;Yao L;Hu Z;Mei H;He Z;Cai Z;Guo Y;Li X;Zhou L;Huang W
上尿路上皮癌(UTUCs)是一种罕见的肿瘤，通常在晚期确诊。由于缺乏准确反映疾病性质和多样性的模型，UTUC病理生物学和临床治疗的研究一直受到阻碍。在这项研究中，一种改进的类器官培养系统被用来产生一个由25个患者来源的UTUC类器官系组成的文库，该文库保留了其亲代肿瘤的组织结构、标记基因表达、基因组景观和基因表达谱。研究表明，UTUC有机化合物对抗癌药物的反应是可以识别的，该模型支持探索新的治疗策略。这项工作提出了一种用于生成患者来源的UTUC器官系的改进方案，该方案可能有助于阐明UTUC的病理生理学并评估这些疾病对个性化药物治疗的各种反应。由于缺乏准确反映上尿路上皮癌(UTUC)疾病性质和多样性的模型，阻碍了对其病理生物学和临床治疗的研究。这项研究展示了一种从临床样本中产生UTUC有机物的有机培养系统。这些器官模型保留了其亲代肿瘤的特征，并支持探索新的治疗策略。
Upper tract urothelial carcinomas (UTUCs) are rare entities that are usually diagnosed at advanced stages. Research on UTUC pathobiology and clinical management has been hampered by the lack of models accurately reflecting disease nature and diversity. In this study, a modified organoid culture system is used to generate a library of 25 patient‐derived UTUC organoid lines retaining the histological architectures, marker gene expressions, genomic landscapes, and gene expression profiles of their parental tumors. The study demonstrates that the responses of UTUC organoids to anticancer drugs can be identified and the model supports the exploration of novel treatment strategies. This work proposes a modified protocol for generating patient‐derived UTUC organoid lines that may help elucidate UTUC pathophysiology and assess the responses of these diseases to various drug therapies in personalized medicine. The lack of models accurately reflecting disease nature and diversity of upper tract urothelial carcinoma (UTUC) impedes the research on its pathobiology and clinical management. This study demonstrates an organoid culture system to generate UTUC organoids from clinical samples. These organoid models retain the characteristics of their parental tumors and support the exploration of novel treatment strategies.
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影响因子：
7
作者：
Ha G;Roth A;Khattra J;Ho J;Yap D;Prentice LM;Melnyk N;McPherson A;Bashashati A;Laks E;Biele J;Ding J;Le A;Rosner J;Shumansky K;Marra MA;Gilks CB;Huntsman DG;McAlpine JN;Aparicio S;Shah SP
通讯作者：
Shah SP
影响因子：
64.5
作者：
Gao D;Vela I;Sboner A;Iaquinta PJ;Karthaus WR;Gopalan A;Dowling C;Wanjala JN;Undvall EA;Arora VK;Wongvipat J;Kossai M;Ramazanoglu S;Barboza LP;Di W;Cao Z;Zhang QF;Sirota I;Ran L;MacDonald TY;Beltran H;Mosquera JM;Touijer KA;Scardino PT;Laudone VP;Curtis KR;Rathkopf DE;Morris MJ;Danila DC;Slovin SF;Solomon SB;Eastham JA;Chi P;Carver B;Rubin MA;Scher HI;Clevers H;Sawyers CL;Chen Y
通讯作者：
Chen Y
影响因子：
14.8
作者：
Drost J;Karthaus WR;Gao D;Driehuis E;Sawyers CL;Chen Y;Clevers H
通讯作者：
Clevers H
影响因子：
11.5
作者：
Audenet, Francois;Isharwal, Sumit;Solit, David B.
通讯作者：
Solit, David B.
影响因子：
45.3
作者：
Ito, Akihiro;Shintaku, Ichiro;Arai, Yoichi
通讯作者：
Arai, Yoichi