科学家描绘肝癌药物基因组学 “蓝图”

中国科学院分子细胞科学卓越创新中心惠利健研究组、中国科学院上海营养与健康研究所李亦学研究组、第二军医大学附属东方肝胆外科医院张海斌研究组以及南京大学医学院附属鼓楼医院施晓雷等取得一项新进展。他们的研究公布了目前最大的肝癌细胞模型库 LIMORE 及最详细的药物基因组学。这一成果发表在 8 月 12 日出版的《癌细胞》上。

为了表征肝癌中药物基因组相互作用的情况，研究人员开发了一种方案，以大约 50% 的成功率建立人肝癌细胞模型，并用 81 个细胞模型生成肝癌模型库（LIMORE）。LIMORE 能够代表原发癌的基因组和转录组异质性。对 LIMORE 药物基因组学领域的研究发现了新的基因—药物关联，包括对肝癌普遍改变的合成致死率。此外，这也为选择索拉非尼响应患者提供了预测性生物标志候选物。LIMORE 为促进肝癌的药物发现提供了丰富的资源。

据了解，肝癌具有高度异质性、预后差以及药物反应差等特征。更好地理解基因改变和药物反应之间的关系将有助于肝癌的精确治疗。

Cancer Cell. 2019 Aug 12;36(2):179-193.e11. doi: 10.1016/j.ccell.2019.07.001. Epub 2019 Aug 1.

A Pharmacogenomic Landscape in Human Liver Cancers.

Qiu Z1, Li H2, Zhang Z1, Zhu Z3, He S4, Wang X5, Wang P6, Qin J7, Zhuang L3, Wang W8, Xie F8, Gu Y8, Zou K2, Li C2, Li C1, Wang C1, Cen J1, Chen X1, Shu Y1, Zhang Z1, Sun L1, Min L1, Fu Y9, Huang X6, Lv H5, Zhou H8, Ji Y10, Zhang Z11, Meng Z3, Shi X12, Zhang H13, Li Y14, Hui L15.

Author information

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.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS:

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

• PMID:

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• 31378681

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• DOI:

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• 10.1016/j.ccell.2019.07.001