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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.
Afiliação
  • Su D; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China. sudan@zjcc.org.cn.
  • Zhang D; Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China. sudan@zjcc.org.cn.
  • Jin J; Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China. sudan@zjcc.org.cn.
  • Ying L; Research and Development Institute of Precision Medicine, 3D Medicines Inc., Shanghai, China.
  • Han M; Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
  • Chen K; Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
  • Li B; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
  • Wu J; Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
  • Xie Z; Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
  • Zhang F; Research and Development Institute of Precision Medicine, 3D Medicines Inc., Shanghai, China.
  • Lin Y; Department of Chemotherapy, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
  • Cheng G; Research and Development Institute of Precision Medicine, 3D Medicines Inc., Shanghai, China.
  • Li JY; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
  • Huang M; Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
  • Wang J; Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
  • Wang K; Research and Development Institute of Precision Medicine, 3D Medicines Inc., Shanghai, China.
  • Zhang J; Department of Breast Surgery, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
  • Li F; Research and Development Institute of Precision Medicine, 3D Medicines Inc., Shanghai, China.
  • Xiong L; Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
  • Futreal A; Research and Development Institute of Precision Medicine, 3D Medicines Inc., Shanghai, China.
  • Mao W; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
Nat Commun ; 10(1): 5076, 2019 11 07.
Article em En | MEDLINE | ID: mdl-31700061
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperazinas / Purinas / Piridinas / Neoplasias Esofágicas / Inibidores de Proteínas Quinases / Carcinoma de Células Escamosas do Esôfago / Aminopiridinas Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperazinas / Purinas / Piridinas / Neoplasias Esofágicas / Inibidores de Proteínas Quinases / Carcinoma de Células Escamosas do Esôfago / Aminopiridinas Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China