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Tytuł pozycji:

Genomic characteristics and drug screening among organoids derived from non‐small cell lung cancer patients

Tytuł:
Genomic characteristics and drug screening among organoids derived from non‐small cell lung cancer patients
Autorzy:
Jing‐Hua Chen
Xiang‐Peng Chu
Jia‐Tao Zhang
Qiang Nie
Wen‐Fang Tang
Jian Su
Hong‐Hong Yan
Hong‐Ping Zheng
Ze‐Xin Chen
Xin Chen
Meng‐Meng Song
Xin Yi
Pan‐Song Li
Yan‐Fang Guan
Gang Li
Chu‐Xia Deng
Rafael Rosell
Yi‐Long Wu
Wen‐Zhao Zhong
Temat:
Consistency analysis
drug screening
non‐small cell lung cancer
patient‐derived organoid
whole exome sequencing
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Źródło:
Thoracic Cancer, Vol 11, Iss 8, Pp 2279-2290 (2020)
Wydawca:
Wiley, 2020.
Rok publikacji:
2020
Kolekcja:
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1759-7714
1759-7706
Relacje:
https://doaj.org/toc/1759-7706; https://doaj.org/toc/1759-7714
DOI:
10.1111/1759-7714.13542
Dostęp URL:
https://doaj.org/article/4c01d0ba7804464ca3f158961a8a89a8  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.4c01d0ba7804464ca3f158961a8a89a8
Czasopismo naukowe
Background Patient‐derived organoid (PDO) models are highly valuable and have potentially widespread clinical applications. However, limited information is available regarding organoid models of non‐small cell lung cancer (NSCLC). This study aimed to characterize the consistency between primary tumors in NSCLC and PDOs and to explore the applications of PDOs as preclinical models to understand and predict treatment response during lung cancer. Methods Fresh tumor samples were harvested for organoid culture. Primary tumor samples and PDOs were analyzed via whole‐exome sequencing. Paired samples were subjected to immunohistochemical analysis. There were 26 antineoplastic drugs tested in the PDOs. Cell viability was assessed using the Cell Titer Glo assay 7–10 days after drug treatment. A heatmap of log‐transformed values of the half‐maximal inhibitory concentrations was generated on the basis of drug responses of PDOs through nonlinear regression (curve fit). A total of 12 patients (stages I–III) were enrolled, and 7 paired surgical tumors and PDOs were analyzed. Results PDOs retained the histological and genetic characteristics of the primary tumors. The concordance between tumors and PDOs in mutations in the top 20 NSCLC‐related genes was >80% in five patients. Sample purity was significantly and positively associated with variant allele frequency (Pearson r = 0.82, P = 0.0005) and chromosome stability. The in vitro response to drug screening with PDOs revealed high correlation with the mutation profiles in the primary tumors. Conclusions PDOs are highly credible models for detecting NSCLC and for prospective prediction of the treatment response for personalized precision medicine. Key points Lung cancer organoid models could save precious time of drug testing on patients, and accurately select anticancer drugs according to the drug sensitivity results, so as to provide a powerful supplement and verification for the gene sequencing.
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