A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology

被引:13
作者
Xu, Xiaoxi [1 ]
Kumari, Rajendra [2 ]
Zhou, Jun [3 ]
Chen, Jing [2 ]
Mao, Binchen [3 ]
Wang, Jingjing [3 ]
Zheng, Meiling [1 ]
Tu, Xiaolong [3 ]
An, Xiaoyu [2 ]
Chen, Xiaobo [1 ]
Zhang, Likun [1 ]
Tian, Xiaoli [4 ]
Wang, Haojie [5 ]
Dong, Xin [5 ]
Bao, Zhengzheng [1 ]
Guo, Sheng [3 ]
Ouyang, Xuesong [3 ]
Shang, Limei [1 ]
Wang, Fei [3 ]
Yan, Xuefei [3 ]
Zhang, Rui [3 ]
Vries, Robert G. J. [6 ,7 ,8 ]
Clevers, Hans [7 ,8 ]
Li, Qi-Xiang [2 ]
机构
[1] Crown Biosci Inc, Beijing, Peoples R China
[2] Crown Biosci Inc, San Diego, CA 92127 USA
[3] Crown Biosci Inc, Taicang City, Jiangsu, Peoples R China
[4] Shanghai Yihao Biol Technol, Shanghai, Peoples R China
[5] Suzhou NeoL Biosci Co LTD, Suzhou, Peoples R China
[6] Hubrecht Organoid Technol HUB, Utrecht, Netherlands
[7] Royal Netherlands Acad Arts & Sci, Oncode Inst, Hubrecht Inst, Utrecht, Netherlands
[8] Univ Med Ctr, Utrecht, Netherlands
关键词
TUMOR XENOGRAFTS; LUNG-CANCER; MODELS; CELLS; RESISTANCE; MUTATIONS; CETUXIMAB; PREDICT;
D O I
10.1371/journal.pone.0279821
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting "biological equivalence or interchangeability" between the two. Here we demonstrate the applications of PDXO biobank for HTS "matrix" screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of >550 matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.
引用
收藏
页数:21
相关论文
共 62 条
[61]   A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab therapy [J].
Zhang, Lianhai ;
Yang, Jie ;
Cai, Jie ;
Song, Xiaoming ;
Deng, Jianyun ;
Huang, Xuesong ;
Chen, Dawei ;
Yang, Mengmeng ;
Wery, Jean-Pierre ;
Li, Shuangxi ;
Wu, Aiwen ;
Li, Ziyu ;
Li, Zhongwu ;
Liu, Yiqiang ;
Chen, Yiyou ;
Li, Qixiang ;
Ji, Jiafu .
SCIENTIFIC REPORTS, 2013, 3
[62]   A subset of esophageal squamous cell carcinoma patient-derived xenografts respond to cetuximab, which is predicted by high EGFR expression and amplification [J].
Zhu, Hanting ;
Wang, Chunyu ;
Wang, Jingjing ;
Chen, Dawei ;
Deng, Jiaying ;
Deng, Jianyun ;
Fan, Jianhong ;
Badakhshi, Harun ;
Huang, Xuesong ;
Zhang, Likun ;
Cai, Jie ;
Guo, Sheng ;
Qian, Wubin ;
Nie, Yongzhan ;
Li, Qixiang ;
Zhao, Kuaile .
JOURNAL OF THORACIC DISEASE, 2018, 10 (09) :5328-5338