Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.
Nat Genet 2018 Oct; 50(10):1399-1411
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.
Lee, Jin-Ku; Liu, Zhaoqi; Sa, Jason K; Shin, Sang; Wang, Jiguang; Bordyuh, Mykola; Cho, Hee Jin; Elliott, Oliver; Chu, Timothy; Choi, Seung Won; Rosenbloom, Daniel I S; Lee, In-Hee; Shin, Yong Jae; Kang, Hyun Ju; Kim, Donggeon; Kim, Sun Young; Sim, Moon-Hee; Kim, Jusun; Lee, Taehyang; Seo, Yun Jee; Shin, Hyemi; Lee, Mijeong; Kim, Sung Heon; Kwon, Yong-Jun; Oh, Jeong-Woo; Song, Minsuk; Kim, Misuk; Kong, Doo-Sik; Choi, Jung Won; Seol, Ho Jun; Lee, Jung-Il; Kim, Seung Tae; Park, Joon Oh; Kim, Kyoung-Mee; Song, Sang-Yong; Lee, Jeong-Won; Kim, Hee-Cheol; Lee, Jeong Eon; Choi, Min Gew; Seo, Sung Wook; Shim, Young Mog; Zo, Jae Ill; Jeong, Byong Chang; Yoon, Yeup; Ryu, Gyu Ha; Kim, Nayoung K D; Bae, Joon Seol; Park, Woong-Yang; Lee, Jeongwu; Verhaak, Roel G W; Iavarone, Antonio; Lee, Jeeyun; Rabadan, Raul; and Nam, Do-Hyun, "Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy." (2018). Faculty Research 2018. 205.