2015
DOI: 10.1158/1535-7163.mct-15-0050
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Abstract: Patients with non-small cell lung cancer (NSCLC) EGFR mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitors. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 … Show more

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Cited by 53 publications
(57 citation statements)
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References 42 publications
(55 reference statements)
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“…Epithelial-mesenchymal transition (EMT) phenotype, loss of epithelial characteristics (E-cadherin), and acquisition of mesenchymal properties (vimentin, fibronectin, or N-cadherin), have been shown to play a crucial role in drug resistance of cancer cells against conventional therapeutics including taxane, vincristine, oxaliplatin, as well as epidermal growth factor receptor (EGFR)-targeted agents (23)(24)(25). Cancer stem cell (CSC) features also contribute to this drug resistance (26,27). CSCs drive both continued expansion of malignant cells and resistance to chemotherapy (28)(29)(30).…”
Section: Introductionmentioning
confidence: 99%
“…Epithelial-mesenchymal transition (EMT) phenotype, loss of epithelial characteristics (E-cadherin), and acquisition of mesenchymal properties (vimentin, fibronectin, or N-cadherin), have been shown to play a crucial role in drug resistance of cancer cells against conventional therapeutics including taxane, vincristine, oxaliplatin, as well as epidermal growth factor receptor (EGFR)-targeted agents (23)(24)(25). Cancer stem cell (CSC) features also contribute to this drug resistance (26,27). CSCs drive both continued expansion of malignant cells and resistance to chemotherapy (28)(29)(30).…”
Section: Introductionmentioning
confidence: 99%
“…Cancer cells with CSC-like properties, which are characterized by their capacity for pluripotency and self-renewal, have been attracting interest as a source of cancer cells (23). The therapeutic significance of CSC-like properties has been reported in NSCLC patients (6,7,24,25); however, the prognostic significance of CSC-associated markers remains to be clarified. Embryonic signaling pathways, including Hedgehog, Notch, WNT and B lymphoma MLV insertion region 1, are associated with the renewal of normal stem cells and the maintenance of tissue homeostasis (26).…”
Section: Discussionmentioning
confidence: 99%
“…A previous study demonstrated that CSCs were involved in the acquired resistance to EGFR TKIs in mutant EGFR NSCLC (6). Our group recently reported that overexpression of ABCB1 was associated with CSCs as a mechanism of resistance to mesenchymal-epithelial transition factor (MET) inhibition in NSCLC cells (7). However, the potential correlation between these CSC-associated marker proteins and patient survival remains to be clarified.…”
Section: Introductionmentioning
confidence: 97%
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