Cargando…
Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma
Previous studies from the Cancer Cell Line Encyclopedia (CCLE) project have adopted commercial pan-cancer cell line models to identify drug sensitivity biomarkers. However, drug sensitivity biomarkers in esophageal squamous cell carcinoma (ESCC) have not been widely explored. Here, eight patient-der...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838071/ https://www.ncbi.nlm.nih.gov/pubmed/31700061 http://dx.doi.org/10.1038/s41467-019-12846-7 |
_version_ | 1783467149533118464 |
---|---|
author | Su, Dan Zhang, Dadong Jin, Jiaoyue Ying, Lisha Han, Miao Chen, Kaiyan Li, Bin Wu, Junzhou Xie, Zhenghua Zhang, Fanrong Lin, Yihui Cheng, Guoping Li, Jing-Yu Huang, Minran Wang, Jinchao Wang, Kailai Zhang, Jianjun Li, Fugen Xiong, Lei Futreal, Andrew Mao, Weimin |
author_facet | Su, Dan Zhang, Dadong Jin, Jiaoyue Ying, Lisha Han, Miao Chen, Kaiyan Li, Bin Wu, Junzhou Xie, Zhenghua Zhang, Fanrong Lin, Yihui Cheng, Guoping Li, Jing-Yu Huang, Minran Wang, Jinchao Wang, Kailai Zhang, Jianjun Li, Fugen Xiong, Lei Futreal, Andrew Mao, Weimin |
author_sort | Su, Dan |
collection | PubMed |
description | Previous studies from the Cancer Cell Line Encyclopedia (CCLE) project have adopted commercial pan-cancer cell line models to identify drug sensitivity biomarkers. However, drug sensitivity biomarkers in esophageal squamous cell carcinoma (ESCC) have not been widely explored. Here, eight patient-derived cell lines (PDCs) are successfully established from 123 patients with ESCC. The mutation profiling of PDCs can partially recapture the tumor tissue actionable mutations from 161 patients with ESCC. Based on these mutations and relative pathways in eight PDCs, 46 targeted drugs are selected for screening. Interestingly, some drug and biomarker relationships are established that were not discovered in the CCLE project. For example, CDKN2A or CDKN2B loss is significantly associated with the sensitivity of CDK4/6 inhibitors. Furthermore, both PDC xenografts and patient-derived xenografts confirm CDKN2A/2B loss as a biomarker predictive of CDK4/6 inhibitor sensitivity. Collectively, patient-derived models could predict targeted drug sensitivity associated with actionable mutations in ESCC. |
format | Online Article Text |
id | pubmed-6838071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68380712019-11-12 Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma Su, Dan Zhang, Dadong Jin, Jiaoyue Ying, Lisha Han, Miao Chen, Kaiyan Li, Bin Wu, Junzhou Xie, Zhenghua Zhang, Fanrong Lin, Yihui Cheng, Guoping Li, Jing-Yu Huang, Minran Wang, Jinchao Wang, Kailai Zhang, Jianjun Li, Fugen Xiong, Lei Futreal, Andrew Mao, Weimin Nat Commun Article Previous studies from the Cancer Cell Line Encyclopedia (CCLE) project have adopted commercial pan-cancer cell line models to identify drug sensitivity biomarkers. However, drug sensitivity biomarkers in esophageal squamous cell carcinoma (ESCC) have not been widely explored. Here, eight patient-derived cell lines (PDCs) are successfully established from 123 patients with ESCC. The mutation profiling of PDCs can partially recapture the tumor tissue actionable mutations from 161 patients with ESCC. Based on these mutations and relative pathways in eight PDCs, 46 targeted drugs are selected for screening. Interestingly, some drug and biomarker relationships are established that were not discovered in the CCLE project. For example, CDKN2A or CDKN2B loss is significantly associated with the sensitivity of CDK4/6 inhibitors. Furthermore, both PDC xenografts and patient-derived xenografts confirm CDKN2A/2B loss as a biomarker predictive of CDK4/6 inhibitor sensitivity. Collectively, patient-derived models could predict targeted drug sensitivity associated with actionable mutations in ESCC. Nature Publishing Group UK 2019-11-07 /pmc/articles/PMC6838071/ /pubmed/31700061 http://dx.doi.org/10.1038/s41467-019-12846-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Su, Dan Zhang, Dadong Jin, Jiaoyue Ying, Lisha Han, Miao Chen, Kaiyan Li, Bin Wu, Junzhou Xie, Zhenghua Zhang, Fanrong Lin, Yihui Cheng, Guoping Li, Jing-Yu Huang, Minran Wang, Jinchao Wang, Kailai Zhang, Jianjun Li, Fugen Xiong, Lei Futreal, Andrew Mao, Weimin Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma |
title | Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma |
title_full | Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma |
title_fullStr | Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma |
title_full_unstemmed | Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma |
title_short | Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma |
title_sort | identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838071/ https://www.ncbi.nlm.nih.gov/pubmed/31700061 http://dx.doi.org/10.1038/s41467-019-12846-7 |
work_keys_str_mv | AT sudan identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT zhangdadong identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT jinjiaoyue identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT yinglisha identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT hanmiao identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT chenkaiyan identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT libin identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT wujunzhou identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT xiezhenghua identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT zhangfanrong identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT linyihui identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT chengguoping identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT lijingyu identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT huangminran identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT wangjinchao identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT wangkailai identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT zhangjianjun identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT lifugen identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT xionglei identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT futrealandrew identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma AT maoweimin identificationofpredictorsofdrugsensitivityusingpatientderivedmodelsofesophagealsquamouscellcarcinoma |