Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.
Document Type
Article
Publication Date
10-2018
JAX Source
Nat Genet 2018 Oct; 50(10):1399-1411
Volume
50
Issue
10
First Page
1399
Last Page
1411
ISSN
1546-1718
PMID
30262818
DOI
https://doi.org/10.1038/s41588-018-0209-6
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.
Recommended Citation
Lee J,
Liu Z,
Sa J,
Shin S,
Wang J,
Bordyuh M,
Cho H,
Elliott O,
Chu T,
Choi S,
Rosenbloom D,
Lee I,
Shin Y,
Kang H,
Kim D,
Kim S,
Sim M,
Kim J,
Lee T,
Seo Y,
Shin H,
Lee M,
Kim S,
Kwon Y,
Oh J,
Song M,
Kim M,
Kong D,
Choi J,
Seol H,
Lee J,
Kim S,
Park J,
Kim K,
Song S,
Lee J,
Kim H,
Lee J,
Choi M,
Seo S,
Shim Y,
Zo J,
Jeong B,
Yoon Y,
Ryu G,
Kim N,
Bae J,
Park W,
Lee J,
Verhaak R,
Iavarone A,
Lee J,
Rabadan R,
Nam D.
Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy. Nat Genet 2018 Oct; 50(10):1399-1411