A Pharmacogenomic Landscape in Human Liver Cancers

人类肝癌的药物基因组学概况

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作者:Zhixin Qiu, Hong Li, Zhengtao Zhang, Zhenfeng Zhu, Sheng He, Xujun Wang, Pengcheng Wang, Jianjie Qin, Liping Zhuang, Wei Wang, Fubo Xie, Ying Gu, Keke Zou, Chao Li, Chun Li, Chenhua Wang, Jin Cen, Xiaotao Chen, Yajing Shu, Zhao Zhang, Lulu Sun, Lihua Min, Yong Fu, Xiaowu Huang, Hui Lv, He Zhou, Yuan

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.

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