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MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer.
Yang, Yang; Wu, Nandie; Shen, Jie; Teixido, Cristina; Sun, Xia; Lin, Zihan; Qian, Xiaoping; Zou, Zhengyun; Guan, Wenxian; Yu, Lixia; Rosell, Rafael; Liu, Baorui; Wei, Jia.
Afiliação
  • Yang Y; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • Wu N; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • Shen J; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • Teixido C; Pangaea Biotech, USP Dexeus University Institute, Barcelona, Spain.
  • Sun X; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • Lin Z; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • Qian X; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • Zou Z; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • Guan W; Department of General Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
  • Yu L; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • Rosell R; Pangaea Biotech, USP Dexeus University Institute, Barcelona, Spain.
  • Liu B; Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Medical Oncology Service, Badalona, Spain.
  • Wei J; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Gastric Cancer ; 19(3): 778-88, 2016 Jul.
Article em En | MEDLINE | ID: mdl-26404902
BACKGROUND: Currently, only trastuzumab, ramucirumab, and apatinib effectively treat gastric cancer. Thus, additional novel targets are required for this disease. METHODS: We investigated the immunohistochemical and fluorescence in situ hybridization expression of MET, ROS1, and ALK in four gastric cell lines and a cohort of 98 gastric cancer patients. Crizotinib response was studied in vitro and in vivo. RESULTS: Crizotinib potently inhibited in vitro cell growth in only one cell line, which also showed MET amplification. A positive correlation between crizotinib sensitivity and MET overexpression was observed (P = 0.045) in the histoculture drug response assay. Meanwhile, patient-derived tumor xenograft mouse models transplanted with tissues with higher MET protein expression displayed a highly selective sensitivity to crizotinib. In the 98 patients, MET overexpression was found in 42 (42.9 %) and MET was amplified in 4 (4.1 %). ROS1 and ALK overexpression were found in 25 (25.5 %) and 0 patients, respectively. However, none of the patients screened harbored ALK or ROS1 rearrangements. No significant association was found between overall survival and MET or ROS1 status. We also observed a stage IV gastric cancer patient with MET amplification who experienced tumor shrinkage and clinical benefit after 3 weeks of crizotinib as fourth-line treatment. CONCLUSIONS: Crizotinib may induce clinically relevant anticancer effects in MET-overexpressed or MET-amplified gastric cancer patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazóis / Piridinas / Neoplasias Gástricas / Biomarcadores Tumorais / Resistencia a Medicamentos Antineoplásicos / Proteínas Proto-Oncogênicas c-met / Inibidores de Proteínas Quinases Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazóis / Piridinas / Neoplasias Gástricas / Biomarcadores Tumorais / Resistencia a Medicamentos Antineoplásicos / Proteínas Proto-Oncogênicas c-met / Inibidores de Proteínas Quinases Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article