@article{3a1f7bb6f90949ee984f6ad2df8b3e6d,
title = "A Pharmacogenomic Landscape in Human Liver Cancers",
abstract = "Liver cancers are highly heterogeneous with poor prognosis and drug response. A better understanding between genetic alterations and drug responses would facilitate precision treatment for liver cancers. To characterize the landscape of pharmacogenomic interactions in liver cancers, we developed a protocol to establish human liver cancer cell models at a success rate of around 50% and generated the Liver Cancer Model Repository (LIMORE) with 81 cell models. LIMORE represented genomic and transcriptomic heterogeneity of primary cancers. Interrogation of the pharmacogenomic landscape of LIMORE discovered unexplored gene-drug associations, including synthetic lethalities to prevalent alterations in liver cancers. Moreover, predictive biomarker candidates were suggested for the selection of sorafenib-responding patients. LIMORE provides a rich resource facilitating drug discovery in liver cancers. Qiu et al. establish the Liver Cancer Model Repository, combining public and newly generated cell lines, which represents genomic and transcriptomic heterogeneity of Eastern Asian hepatocellular carcinomas, and use it to reveal gene-drug associations and potential biomarkers for selecting sorafenib-responding patients.",
keywords = "liver cancer, patient-derived cancer models, pharmacogenomics, sorafenib",
author = "Zhixin Qiu and Hong Li and Zhengtao Zhang and Zhenfeng Zhu and S. He and X. Wang and Pengcheng Wang and Jianjie Qin and Liping Zhuang and Wei Wang and Fubo Xie and Ying Gu and Keke Zou and Chao Li and Chun Li and Chenhua Wang and Jin Cen and Xiaotao Chen and Yajing Shu and Zhao Zhang and Lulu Sun and L. Min and Yong Fu and Xiaowu Huang and Hui Lv and He Zhou and Yuan Ji and Zhigang Zhang and Zhiqiang Meng and Xiaolei Shi and Haibin Zhang and Y. Li and Lijian Hui",
note = "Funding Information: We thank Xiang Chen (St. Jude Children's Research Hospital), Xiangsheng Ye (Eli Lilly and Company), and Hai Jiang (Shanghai Institute of Biochemistry and Cell Biology [SIBCB]) for critical reading and suggestions. We thank Chemical Biology Core Facility at SIBCB for technical assistance in drug screening. This study is supported by Chinese Academy of Sciences (XDA16020201 and XDA12050104), the National Natural Science Foundation of China (31630044, 81703093, and 31801228), Science and Technology Commission of Shanghai Municipality (16JC1400202), National Major Science and Technology Projects of China (2018ZX09711002-009), and National Special Support Plan for Top Talents. Conceptualization, Z.Q. and L.H.; Methodology, Z.Q, H. Li, Zhengtao Zhang, Zhigang Zhang, and L.Z.; Software, H. Li, X.W. K.Z. Chao Li, and H. Lv; Experiments, Z.Q. Zhengtao Zhang, Zhenfeng Zhu, P.W. L.Z. W.W. F.X. Y.G. J.C. Chun Li, C.W. Y.S. Zhao Zhang, L.S. and Y.F.; Sample and Histology, J.Q. X.H. Z.M. X.S. H. Zhang, and Y.J.; Data Curation, Z.Q. H. Li, Zhengtao Zhang, S.H. and X.C.; Writing, Z.Q. L.H. Zhengtao Zhang, H. Li, Y.L. H. Zhang, L.M. and H. Zhou; Supervision, L.H. Y.L. and H. Zhang. H. Zhou, W.W. F.X. and Y.G. are employees of Shanghai ChemPartner Co. Ltd. The remaining authors declare no competing interests. Funding Information: We thank Xiang Chen (St. Jude Children's Research Hospital), Xiangsheng Ye (Eli Lilly and Company), and Hai Jiang (Shanghai Institute of Biochemistry and Cell Biology [SIBCB]) for critical reading and suggestions. We thank Chemical Biology Core Facility at SIBCB for technical assistance in drug screening. This study is supported by Chinese Academy of Sciences ( XDA16020201 and XDA12050104 ), the National Natural Science Foundation of China ( 31630044 , 81703093 , and 31801228 ), Science and Technology Commission of Shanghai Municipality ( 16JC1400202 ), National Major Science and Technology Projects of China ( 2018ZX09711002-009 ), and National Special Support Plan for Top Talents . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = aug,
day = "12",
doi = "10.1016/j.ccell.2019.07.001",
language = "English (US)",
volume = "36",
pages = "179--193.e11",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}