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- W2974668768 abstract "The AXL receptor tyrosine kinase is involved in signal transduction in malignant cells. Recent studies have shown that the AXL upregulation underlies epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance in EGFR-mutant non-small cell lung cancer (NSCLC). In this study, we investigated the effect of DS-1205b, a novel and selective inhibitor of AXL, on tumor growth and resistance to EGFR TKIs. In AXL-overexpressing NIH3T3 cells, DS-1205b potently inhibited hGAS6 ligand-induced migration in vitro and exerted significant antitumor activity in vivo. AXL was upregulated by long-term erlotinib or osimertinib treatment in HCC827 EGFR-mutant NSCLC cells, and DS-1205b treatment in combination with osimertinib or erlotinib effectively inhibited signaling downstream of EGFR in a cell-based assay. In an HCC827 EGFR-mutant NSCLC xenograft mouse model, combination treatment with DS-1205b and erlotinib significantly delayed the onset of tumor resistance compared to erlotinib monotherapy, and DS-1205b restored the antitumor activity of erlotinib in erlotinib-resistant tumors. DS-1205b also delayed the onset of resistance when used in combination with osimertinib in the model. These findings strongly suggest that DS-1205b can prolong the therapeutic benefit of EGFR TKIs in nonclinical as well as clinical settings." @default.
- W2974668768 created "2019-09-26" @default.
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- W2974668768 date "2019-08-27" @default.
- W2974668768 modified "2023-10-18" @default.
- W2974668768 title "DS-1205b, a novel selective inhibitor of AXL kinase, blocks resistance to EGFR-tyrosine kinase inhibitors in a non-small cell lung cancer xenograft model" @default.
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- W2974668768 doi "https://doi.org/10.18632/oncotarget.27114" @default.
- W2974668768 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6718264" @default.
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