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Patient-Derived Cells to Guide Targeted Therapy for Advanced Lung Adenocarcinoma

Authors
 Seok-Young Kim  ;  Ji Yeon Lee  ;  Dong Hwi Kim  ;  Hyeong -Seok Joo  ;  Mi Ran Yun  ;  Dongmin Jung  ;  Jiyeon Yun  ;  Seong Gu Heo  ;  Beung -Chul Ahn  ;  Chae Won Park  ;  Kyoung Ho Pyo  ;  You Jin Chun  ;  Min Hee Hong  ;  Hye Ryun Kim  ;  Byoung Chul Cho 
Citation
 SCIENTIFIC REPORTS, Vol.9(1) : 19909, 2019 
Journal Title
 SCIENTIFIC REPORTS 
Issue Date
2019
Abstract
Adequate preclinical model and model establishment procedure are required to accelerate translational research in lung cancer. We streamlined a protocol for establishing patient-derived cells (PDC) and identified effective targeted therapies and novel resistance mechanisms using PDCs. We generated 23 PDCs from 96 malignant effusions of 77 patients with advanced lung adenocarcinoma. Clinical and experimental factors were reviewed to identify determinants for PDC establishment. PDCs were characterized by driver mutations and in vitro sensitivity to targeted therapies. Seven PDCs were analyzed by whole-exome sequencing. PDCs were established at a success rate of 24.0%. Utilizing cytological diagnosis and tumor colony formation can improve the success rate upto 48.8%. In vitro response to a tyrosine kinase inhibitor (TKI) in PDC reflected patient treatment response and contributed to identifying effective therapies. Combination of dabrafenib and trametinib was potent against a rare BRAF K601E mutation. Afatinib was the most potent EGFR-TKI against uncommon EGFR mutations including L861Q, G719C/S768I, and D770_N771insG. Aurora kinase A (AURKA) was identified as a novel resistance mechanism to olmutinib, a mutant-selective, third-generation EGFR-TKI, and inhibition of AURKA overcame the resistance. We presented an efficient protocol for establishing PDCs. PDCs empowered precision medicine with promising translational values.
Files in This Item:
T201905762.pdf Download
DOI
10.1038/s41598-019-56356-4
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Ahn, Beung-Chul(안병철) ORCID logo https://orcid.org/0000-0002-2579-2791
Yun, Mi Ran(윤미란)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Pyo, Kyoung Ho(표경호) ORCID logo https://orcid.org/0000-0001-5428-0288
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174867
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