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Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography...
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| Zeitschriftentitel: | Clinical Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | Clinical Cancer Research, 20, 2014, 18, S. 4806-4815 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Iommelli, Francesca De Rosa, Viviana Gargiulo, Sara Panico, Mariarosaria Monti, Marcello Greco, Adelaide Gramanzini, Matteo Ortosecco, Giovanni Fonti, Rosa Brunetti, Arturo Del Vecchio, Silvana Iommelli, Francesca De Rosa, Viviana Gargiulo, Sara Panico, Mariarosaria Monti, Marcello Greco, Adelaide Gramanzini, Matteo Ortosecco, Giovanni Fonti, Rosa Brunetti, Arturo Del Vecchio, Silvana |
|---|---|
| author |
Iommelli, Francesca De Rosa, Viviana Gargiulo, Sara Panico, Mariarosaria Monti, Marcello Greco, Adelaide Gramanzini, Matteo Ortosecco, Giovanni Fonti, Rosa Brunetti, Arturo Del Vecchio, Silvana |
| spellingShingle |
Iommelli, Francesca De Rosa, Viviana Gargiulo, Sara Panico, Mariarosaria Monti, Marcello Greco, Adelaide Gramanzini, Matteo Ortosecco, Giovanni Fonti, Rosa Brunetti, Arturo Del Vecchio, Silvana Clinical Cancer Research Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography Cancer Research Oncology |
| author_sort |
iommelli, francesca |
| spelling |
Iommelli, Francesca De Rosa, Viviana Gargiulo, Sara Panico, Mariarosaria Monti, Marcello Greco, Adelaide Gramanzini, Matteo Ortosecco, Giovanni Fonti, Rosa Brunetti, Arturo Del Vecchio, Silvana 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-14-0264 <jats:title>Abstract</jats:title> <jats:p>Purpose: MET amplification is one of the mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non–small cell lung cancer (NSCLC). Here, we tested whether 3′-deoxy-3′-[18F]-fluorothymidine ([18F]FLT) positron emission tomography/computerized tomography (PET/CT) can detect MET-mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in NSCLC.</jats:p> <jats:p>Experimental Design: H1993 and H820 NSCLC cells with high and low levels of MET amplification, respectively, and HCC827-expressing MET, but without gene amplification, were tested for the effects of MET inhibitors on the EGFR pathway and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and without MET amplification were subjected to [18F]FLT PET/CT before and after treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days).</jats:p> <jats:p>Results: H1993 cells showed high responsiveness to MET inhibitors and were resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [18F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [18F]FLT uptake were observed in HCC827 tumors lacking MET amplification. Furthermore, a persistently high [18F]FLT uptake was observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors showed up to 39% reduction of [18F]FLT uptake following erlotinib treatment. Imaging findings were confirmed by Ki67 immunostaining of tumor sections.</jats:p> <jats:p>Conclusions: [18F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs and its reversal by MET inhibitors in NSCLC. Clin Cancer Res; 20(18); 4806–15. ©2014 AACR.</jats:p> Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography Clinical Cancer Research |
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10.1158/1078-0432.ccr-14-0264 |
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American Association for Cancer Research (AACR), 2014 |
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American Association for Cancer Research (AACR), 2014 |
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1078-0432 1557-3265 |
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| title |
Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_unstemmed |
Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_full |
Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_fullStr |
Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_full_unstemmed |
Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_short |
Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_sort |
monitoring reversal of met-mediated resistance to egfr tyrosine kinase inhibitors in non–small cell lung cancer using 3′-deoxy-3′-[18f]-fluorothymidine positron emission tomography |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1078-0432.ccr-14-0264 |
| publishDate |
2014 |
| physical |
4806-4815 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Purpose: MET amplification is one of the mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non–small cell lung cancer (NSCLC). Here, we tested whether 3′-deoxy-3′-[18F]-fluorothymidine ([18F]FLT) positron emission tomography/computerized tomography (PET/CT) can detect MET-mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in NSCLC.</jats:p>
<jats:p>Experimental Design: H1993 and H820 NSCLC cells with high and low levels of MET amplification, respectively, and HCC827-expressing MET, but without gene amplification, were tested for the effects of MET inhibitors on the EGFR pathway and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and without MET amplification were subjected to [18F]FLT PET/CT before and after treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days).</jats:p>
<jats:p>Results: H1993 cells showed high responsiveness to MET inhibitors and were resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [18F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [18F]FLT uptake were observed in HCC827 tumors lacking MET amplification. Furthermore, a persistently high [18F]FLT uptake was observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors showed up to 39% reduction of [18F]FLT uptake following erlotinib treatment. Imaging findings were confirmed by Ki67 immunostaining of tumor sections.</jats:p>
<jats:p>Conclusions: [18F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs and its reversal by MET inhibitors in NSCLC. Clin Cancer Res; 20(18); 4806–15. ©2014 AACR.</jats:p> |
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| description | <jats:title>Abstract</jats:title> <jats:p>Purpose: MET amplification is one of the mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non–small cell lung cancer (NSCLC). Here, we tested whether 3′-deoxy-3′-[18F]-fluorothymidine ([18F]FLT) positron emission tomography/computerized tomography (PET/CT) can detect MET-mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in NSCLC.</jats:p> <jats:p>Experimental Design: H1993 and H820 NSCLC cells with high and low levels of MET amplification, respectively, and HCC827-expressing MET, but without gene amplification, were tested for the effects of MET inhibitors on the EGFR pathway and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and without MET amplification were subjected to [18F]FLT PET/CT before and after treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days).</jats:p> <jats:p>Results: H1993 cells showed high responsiveness to MET inhibitors and were resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [18F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [18F]FLT uptake were observed in HCC827 tumors lacking MET amplification. Furthermore, a persistently high [18F]FLT uptake was observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors showed up to 39% reduction of [18F]FLT uptake following erlotinib treatment. Imaging findings were confirmed by Ki67 immunostaining of tumor sections.</jats:p> <jats:p>Conclusions: [18F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs and its reversal by MET inhibitors in NSCLC. Clin Cancer Res; 20(18); 4806–15. ©2014 AACR.</jats:p> |
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| spelling | Iommelli, Francesca De Rosa, Viviana Gargiulo, Sara Panico, Mariarosaria Monti, Marcello Greco, Adelaide Gramanzini, Matteo Ortosecco, Giovanni Fonti, Rosa Brunetti, Arturo Del Vecchio, Silvana 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-14-0264 <jats:title>Abstract</jats:title> <jats:p>Purpose: MET amplification is one of the mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non–small cell lung cancer (NSCLC). Here, we tested whether 3′-deoxy-3′-[18F]-fluorothymidine ([18F]FLT) positron emission tomography/computerized tomography (PET/CT) can detect MET-mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in NSCLC.</jats:p> <jats:p>Experimental Design: H1993 and H820 NSCLC cells with high and low levels of MET amplification, respectively, and HCC827-expressing MET, but without gene amplification, were tested for the effects of MET inhibitors on the EGFR pathway and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and without MET amplification were subjected to [18F]FLT PET/CT before and after treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days).</jats:p> <jats:p>Results: H1993 cells showed high responsiveness to MET inhibitors and were resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [18F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [18F]FLT uptake were observed in HCC827 tumors lacking MET amplification. Furthermore, a persistently high [18F]FLT uptake was observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors showed up to 39% reduction of [18F]FLT uptake following erlotinib treatment. Imaging findings were confirmed by Ki67 immunostaining of tumor sections.</jats:p> <jats:p>Conclusions: [18F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs and its reversal by MET inhibitors in NSCLC. Clin Cancer Res; 20(18); 4806–15. ©2014 AACR.</jats:p> Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography Clinical Cancer Research |
| spellingShingle | Iommelli, Francesca, De Rosa, Viviana, Gargiulo, Sara, Panico, Mariarosaria, Monti, Marcello, Greco, Adelaide, Gramanzini, Matteo, Ortosecco, Giovanni, Fonti, Rosa, Brunetti, Arturo, Del Vecchio, Silvana, Clinical Cancer Research, Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography, Cancer Research, Oncology |
| title | Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_full | Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_fullStr | Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_full_unstemmed | Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_short | Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| title_sort | monitoring reversal of met-mediated resistance to egfr tyrosine kinase inhibitors in non–small cell lung cancer using 3′-deoxy-3′-[18f]-fluorothymidine positron emission tomography |
| title_unstemmed | Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1078-0432.ccr-14-0264 |