作者: Yuichi Sesumi , Kenichi Suda , Hiroshi Mizuuchi , Yoshihisa Kobayashi , Katsuaki Sato
DOI: 10.1016/J.LUNGCAN.2016.12.012
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摘要: Abstract Objective The epithelial to mesenchymal transition (EMT) is associated with acquired resistance epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor EGFR mutations. Because no currently available drugs specifically kill cancer cells via EMT, novel treatment strategies overcome or prevent EMT are needed. A recent report suggested dasatinib (an ABL/Src inhibitor) inhibits induced by transforming (TGF)-beta (Wilson et al., 2014). In this study, we analyzed effects of on the mechanism HCC4006 cells, which tend acquire EGFR-TKIs EMT. Materials and methods Sensitivity erlotinib-resistant (ER) an phenotype was analyzed. against combination erlotinib (HCC4006EDR) following chronic these drugs. expression markers were Results Short-term long-term did not reverse HCC4006ER. contrast, HCC4006EDR maintained phenotype, underlying plus therapy attributable a T790M secondary mutation. but HCC4006ER highly sensitive third-generation EGFR-TKI, osimertinib. Conclusions Although monotherapy preemptive prevented emergence led T790M. Our results indicate may be promising strategy EMT-mediated resistance.