A Pharmacogenomic Landscape in Human Liver Cancers

Zhixin Qiu, Hong Li, Zhengtao Zhang, Zhenfeng Zhu, S. He, X. 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 ZhangLulu Sun, L. Min, Yong Fu, Xiaowu Huang, Hui Lv, He Zhou, Yuan Ji, Zhigang Zhang, Zhiqiang Meng, Xiaolei Shi, Haibin Zhang, Y. Li, Lijian Hui

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)179-193.e11
JournalCancer Cell
Volume36
Issue number2
DOIs
StatePublished - Aug 12 2019
Externally publishedYes

Keywords

  • liver cancer
  • patient-derived cancer models
  • pharmacogenomics
  • sorafenib

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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