Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.

Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.
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患者衍生的肿瘤细胞的药物基因组景观为精度肿瘤疗法提供了信息。

DOI：
10.1038/s41588-018-0209-6
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发表时间：
2018-10
期刊：
Nature genetics
影响因子：
30.8
通讯作者：
Nam DH
Nam DH
中科院分区：
生物学1区
文献类型：
--
作者：
Lee JK;Liu Z;Sa JK;Shin S;Wang J;Bordyuh M;Cho HJ;Elliott O;Chu T;Choi SW;Rosenbloom DIS;Lee IH;Shin YJ;Kang HJ;Kim D;Kim SY;Sim MH;Kim J;Lee T;Seo YJ;Shin H;Lee M;Kim SH;Kwon YJ;Oh JW;Song M;Kim M;Kong DS;Choi JW;Seol HJ;Lee JI;Kim ST;Park JO;Kim KM;Song SY;Lee JW;Kim HC;Lee JE;Choi MG;Seo SW;Shim YM;Zo JI;Jeong BC;Yoon Y;Ryu GH;Kim NKD;Bae JS;Park WY;Lee J;Verhaak RGW;Iavarone A;Lee J;Rabadan R;Nam DH
来源链接：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514738/

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由于不同的遗传和分子背景，抗癌治疗的结果在患者之间差异很大，突出了广泛的肿瘤间异质性。精确肿瘤学的基本原则定义了肿瘤的分子特征，以指导最佳的患者定制治疗。为了实现这一目标，我们已经建立了14种癌症类型的462个患者源性肿瘤细胞（PDC）的药理学景观汇编，以及其中385个肿瘤的基因组和转录组学分析。与传统的长期培养的肿瘤细胞系模型相比，PDCs更准确地再现了疾病的分子特征和生物学特性。在本研究中，我们提供了前所未有的动态药物基因组学关联的见解，包括引发EGFR抑制剂治疗耐药性的分子决定因素和伊曲替尼（目前用于血液恶性肿瘤）用于胶质瘤EGFR特异性治疗的潜在再利用。最后，我们利用回顾性临床研究提出了PDC衍生药物敏感性的潜在实施，以预测对靶向治疗的临床反应。
Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive inter-tumoral heterogeneity. The fundamental tenet of precision oncology defines molecular characterization of tumors to guide optimal patient-tailored therapy. Towards this goal, we have established a compilation of pharmacological landscape of 462 patient-derived tumor cells (PDCs) across 14 cancer types, together with genomic and transcriptomic profiling in 385 of these tumors. Compared to the traditional long-term cultured cancer cell-line models, PDCs recapitulate the molecular properties and biology of the diseases more precisely. In present study, we provide unprecedented insights into dynamic pharmacogenomic associations, including molecular determinants that elicit therapeutic resistance to EGFR inhibitors and potential repurposing of ibrutinib (currently being used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, we present potential implementation of PDC-derived drug sensitivities for prediction of clinical response to targeted therapeutics using retrospective clinical studies.
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