Abstract 879: Investigating the activity of neratinib in human gastric cancer and gastric cancer cells, implications on clinical outcome and chemotherapy resistance
Cancer Research(2018)
摘要
Background. The EGF receptor (EGFR) kinase family plays important role in tumour growth and progression and has been a validated therapeutic target for lung cancers. Here, we examined the activity of an irreversible pan-HER tyrosine kinase inhibitor, neratinib, on kinase phosphorylation and cellular response in human gastric cancer. The study also examined the expression of the neratinib responsive kinases in relation to chemoresistance in human gastric cancer. Method. Tumour and normal gastric tissues from a cohort of 85 patients were obtained along with clinical outcome and therapeutic response to chemotherapy. The level of expression of a panel of protein kinases of interest, including EGFR family members, was quantitatively analysed using a protein based kinase array. Human gastric cancer cells (AGS and HGC27) were assessed for their sensitivity to neratinib, inhibitors of other candidate kinases and combinations thereof. Cellular growth, migration and matrix adhesiveness were evaluated using multiple in vitro platforms. Result. We identified a panel of kinases that were highly responsive to the treatment by neratinib in cell lines. In the gastric cancer cohort, expression of these kinases significantly correlated with the overall survival of the patients (p Citation Format: W. G. Jiang, Tracey A. Martin, Sioned Owen, Lin Ye, Andrew J. Sanders, Yuxin Cui, Meng Xie, Shiqin Jia, Yongning Jia, Fiona Ruge, Francesca Avogadri-Connors, Alshad S. Lalani, Richard P. Bryce, Jiafu Ji. Investigating the activity of neratinib in human gastric cancer and gastric cancer cells, implications on clinical outcome and chemotherapy resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 879.
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