| Literature DB >> 30262818 |
Jin-Ku Lee1,2,3, Zhaoqi Liu4,5, Jason K Sa1,3, Sang Shin1,6, Jiguang Wang7,8,9, Mykola Bordyuh4,5, Hee Jin Cho1,3, Oliver Elliott4,5, Timothy Chu4,5, Seung Won Choi1,6, Daniel I S Rosenbloom4,5, In-Hee Lee1,3, Yong Jae Shin1,2,3, Hyun Ju Kang1,3, Donggeon Kim1,3, Sun Young Kim10, Moon-Hee Sim10, Jusun Kim10, Taehyang Lee10, Yun Jee Seo1,3, Hyemi Shin1,6, Mijeong Lee1,6, Sung Heon Kim1,2, Yong-Jun Kwon1, Jeong-Woo Oh1,6, Minsuk Song1, Misuk Kim1,3, Doo-Sik Kong2, Jung Won Choi2, Ho Jun Seol2, Jung-Il Lee2, Seung Tae Kim10, Joon Oh Park6,10, Kyoung-Mee Kim11, Sang-Yong Song11, Jeong-Won Lee12, Hee-Cheol Kim13, Jeong Eon Lee13, Min Gew Choi13, Sung Wook Seo14, Young Mog Shim15, Jae Ill Zo15, Byong Chang Jeong16, Yeup Yoon3,6, Gyu Ha Ryu3, Nayoung K D Kim3,17, Joon Seol Bae3,17, Woong-Yang Park3,6,17, Jeongwu Lee18, Roel G W Verhaak19, Antonio Iavarone20,21,22, Jeeyun Lee23,24, Raul Rabadan25,26, Do-Hyun Nam27,28,29.
Abstract
Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive intertumoral 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 landscapes of 462 patient-derived tumor cells (PDCs) across 14 cancer types, together with genomic and transcriptomic profiling in 385 of these tumors. Compared with the traditional long-term cultured cancer cell line models, PDCs recapitulate the molecular properties and biology of the diseases more precisely. Here, we provide insights into dynamic pharmacogenomic associations, including molecular determinants that elicit therapeutic resistance to EGFR inhibitors, and the potential repurposing of ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, we present a potential implementation of PDC-derived drug sensitivities for the prediction of clinical response to targeted therapeutics using retrospective clinical studies.Entities:
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Year: 2018 PMID： 30262818 DOI： 10.1038/s41588-018-0209-6
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330