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

Jin Ku Lee; Zhaoqi Liu; Jason K. Sa; Sang Shin; Jiguang Wang; Mykola Bordyuh; Hee Jin Cho; Oliver Elliott; Timothy Chu; Seung Won Choi; Daniel I.S. Rosenbloom; In Hee Lee; Yong Jae Shin; Hyun Ju Kang; Donggeon Kim; Sun Young Kim; Moon Hee Sim; Jusun Kim; Taehyang Lee; Yun Jee Seo; Hyemi Shin; Mijeong Lee; Sung Heon Kim; Yong Jun Kwon; Jeong Woo Oh; Minsuk Song; Misuk Kim; Doo Sik Kong; Jung Won Choi; Ho Jun Seol; Jung Il Lee; Seung Tae Kim; Joon Oh Park; Kyoung Mee Kim; Sang Yong Song; Jeong Won Lee; Hee Cheol Kim; Jeong Eon Lee; Min Gew Choi; Sung Wook Seo; Young Mog Shim; Jae Ill Zo; Byong Chang Jeong; Yeup Yoon; Gyu Ha Ryu; Nayoung K.D. Kim; Joon Seol Bae; Woong Yang Park; Jeongwu Lee; Roel G.W. Verhaak; Antonio Iavarone; Jeeyun Lee; Raul Rabadan; Do Hyun Nam

doi:10.1038/s41588-018-0209-6

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

Jin Ku Lee, Zhaoqi Liu, Jason K. Sa, Sang Shin, Jiguang Wang, Mykola Bordyuh, Hee Jin Cho, Oliver Elliott, Timothy Chu, Seung Won Choi, Daniel I.S. Rosenbloom, In Hee Lee, Yong Jae Shin, Hyun Ju Kang, Donggeon Kim, Sun Young Kim, Moon Hee Sim, Jusun Kim, Taehyang Lee, Yun Jee SeoHyemi Shin, Mijeong Lee, Sung Heon Kim, Yong Jun Kwon, Jeong Woo Oh, Minsuk Song, Misuk Kim, Doo Sik Kong, Jung Won Choi, Ho Jun Seol, Jung Il Lee, Seung Tae Kim, Joon Oh Park, Kyoung Mee Kim, Sang Yong Song, Jeong Won Lee, Hee Cheol Kim, Jeong Eon Lee, Min Gew Choi, Sung Wook Seo, Young Mog Shim, Jae Ill Zo, Byong Chang Jeong, Yeup Yoon, Gyu Ha Ryu, Nayoung K.D. Kim, Joon Seol Bae, Woong Yang Park, Jeongwu Lee, Roel G.W. Verhaak, Antonio Iavarone, Jeeyun Lee, Raul Rabadan, Do Hyun Nam

Major in Biomedical Convergence Science & Technology

Research output: Contribution to journal › Article › peer-review

131 Scopus citations

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.

Original language	English
Pages (from-to)	1399-1411
Number of pages	13
Journal	Nature Genetics
Volume	50
Issue number	10
DOIs	https://doi.org/10.1038/s41588-018-0209-6
State	Published - 1 Oct 2018

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Lee, J. K., Liu, Z., Sa, J. K., Shin, S., Wang, J., Bordyuh, M., Cho, H. J., Elliott, O., Chu, T., Choi, S. W., Rosenbloom, D. I. S., Lee, I. H., Shin, Y. J., Kang, H. J., Kim, D., Kim, S. Y., Sim, M. H., Kim, J., Lee, T., ... Nam, D. H. (2018). Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy. Nature Genetics, 50(10), 1399-1411. https://doi.org/10.1038/s41588-018-0209-6

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title = "Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy",

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.",

author = "Lee, {Jin Ku} and Zhaoqi Liu and Sa, {Jason K.} and Sang Shin and Jiguang Wang and Mykola Bordyuh and Cho, {Hee Jin} and Oliver Elliott and Timothy Chu and Choi, {Seung Won} and Rosenbloom, {Daniel I.S.} and Lee, {In Hee} and Shin, {Yong Jae} and Kang, {Hyun Ju} and Donggeon Kim and Kim, {Sun Young} and Sim, {Moon Hee} and Jusun Kim and Taehyang Lee and Seo, {Yun Jee} and Hyemi Shin and Mijeong Lee and Kim, {Sung Heon} and Kwon, {Yong Jun} and Oh, {Jeong Woo} and Minsuk Song and Misuk Kim and Kong, {Doo Sik} and Choi, {Jung Won} and Seol, {Ho Jun} and Lee, {Jung Il} and Kim, {Seung Tae} and Park, {Joon Oh} and Kim, {Kyoung Mee} and Song, {Sang Yong} and Lee, {Jeong Won} and Kim, {Hee Cheol} and Lee, {Jeong Eon} and Choi, {Min Gew} and Seo, {Sung Wook} and Shim, {Young Mog} and Zo, {Jae Ill} and Jeong, {Byong Chang} and Yeup Yoon and Ryu, {Gyu Ha} and Kim, {Nayoung K.D.} and Bae, {Joon Seol} and Park, {Woong Yang} and Jeongwu Lee and Verhaak, {Roel G.W.} and Antonio Iavarone and Jeeyun Lee and Raul Rabadan and Nam, {Do Hyun}",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2018",

month = oct,

day = "1",

doi = "10.1038/s41588-018-0209-6",

language = "English",

volume = "50",

pages = "1399--1411",

journal = "Nature Genetics",

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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 2018, 'Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy', Nature Genetics, vol. 50, no. 10, pp. 1399-1411. https://doi.org/10.1038/s41588-018-0209-6

TY - JOUR

T1 - Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy

AU - Lee, Jin Ku

AU - Liu, Zhaoqi

AU - Sa, Jason K.

AU - Shin, Sang

AU - Wang, Jiguang

AU - Bordyuh, Mykola

AU - Cho, Hee Jin

AU - Elliott, Oliver

AU - Chu, Timothy

AU - Choi, Seung Won

AU - Rosenbloom, Daniel I.S.

AU - Lee, In Hee

AU - Shin, Yong Jae

AU - Kang, Hyun Ju

AU - Kim, Donggeon

AU - Kim, Sun Young

AU - Sim, Moon Hee

AU - Kim, Jusun

AU - Lee, Taehyang

AU - Seo, Yun Jee

AU - Shin, Hyemi

AU - Lee, Mijeong

AU - Kim, Sung Heon

AU - Kwon, Yong Jun

AU - Oh, Jeong Woo

AU - Song, Minsuk

AU - Kim, Misuk

AU - Kong, Doo Sik

AU - Choi, Jung Won

AU - Seol, Ho Jun

AU - Lee, Jung Il

AU - Kim, Seung Tae

AU - Park, Joon Oh

AU - Kim, Kyoung Mee

AU - Song, Sang Yong

AU - Lee, Jeong Won

AU - Kim, Hee Cheol

AU - Lee, Jeong Eon

AU - Choi, Min Gew

AU - Seo, Sung Wook

AU - Shim, Young Mog

AU - Zo, Jae Ill

AU - Jeong, Byong Chang

AU - Yoon, Yeup

AU - Ryu, Gyu Ha

AU - Kim, Nayoung K.D.

AU - Bae, Joon Seol

AU - Park, Woong Yang

AU - Lee, Jeongwu

AU - Verhaak, Roel G.W.

AU - Iavarone, Antonio

AU - Lee, Jeeyun

AU - Rabadan, Raul

AU - Nam, Do Hyun

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41588-018-0209-6

DO - 10.1038/s41588-018-0209-6

M3 - Article

C2 - 30262818

AN - SCOPUS:85054002698

SN - 1061-4036

VL - 50

SP - 1399

EP - 1411

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

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