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

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.Analysis of genomic and transcriptomic data from 462 patient-derived tumor cell (PDC) samples across 14 cancer types, along with pharmacological responses to 60 agents, indicates that PDC-derived drug sensitivities might be predictive of clinical response to targeted therapies.

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

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