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The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer
MET overexpression and the EGFR T790M mutation are both associated with acquired resistance (AR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). We characterized the frequency, underlying molecular mechanisms, and subsequent...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239477/ https://www.ncbi.nlm.nih.gov/pubmed/27259997 http://dx.doi.org/10.18632/oncotarget.9697 |
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author | Gou, Lan-Ying Li, An-Na Yang, Jin-Ji Zhang, Xu-Chao Su, Jian Yan, Hong-Hong Xie, Zhi Lou, Na-Na Liu, Si-Yang Dong, Zhong-Yi Gao, Hong-Fei Zhou, Qing Zhong, Wen-Zhao Xu, Chong-Rui Wu, Yi-Long |
author_facet | Gou, Lan-Ying Li, An-Na Yang, Jin-Ji Zhang, Xu-Chao Su, Jian Yan, Hong-Hong Xie, Zhi Lou, Na-Na Liu, Si-Yang Dong, Zhong-Yi Gao, Hong-Fei Zhou, Qing Zhong, Wen-Zhao Xu, Chong-Rui Wu, Yi-Long |
author_sort | Gou, Lan-Ying |
collection | PubMed |
description | MET overexpression and the EGFR T790M mutation are both associated with acquired resistance (AR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). We characterized the frequency, underlying molecular mechanisms, and subsequent treatment for AR in MET overexpressing NSCLC patients with or without the T790M mutation. The study participants were 207 patients with advanced NSCLC and AR to EGFR-TKIs. The percentages of MET-, T790M- and MET/T790M-positive patients were 20.3% (42/207), 34.8% (72/207) and 6.8% (14/207), respectively. The disease control rate was 100% (5/5) for five patients with MET overexpression who received EGFR-TKIs plus a MET inhibitor. Among the MET/T790M-positive patients, seven received EGFR-TKIs plus a MET inhibitor and four received a T790M inhibitor, but no response was observed. The median post-progression survival (PPS) was 14.1, 24.5, and 10.7 months for MET-overexpressing, T790M-positive and MET/T790M-positive patients, respectively (P=0.044). c-Met, p-Met, ERBB3, and p-ERBB3 were highly expressed in MET-positive and MET/T790M-positive patients, but were poorly expressed in T790M-positive patients. EGFR, p-EGFR, AKT, p-AKT, MAPK, and p-MAPK were highly expressed in all three groups. These results suggest that MET/T790M-positive patients are at higher risk of AR to EGFR-TKIs, and have a worse PPS than patients with only MET overexpression or the T790M mutation alone. Clinical trials are needed to determine the best treatment for patients with both MET overexpression and the EGFR T790M mutation. |
format | Online Article Text |
id | pubmed-5239477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-52394772017-01-24 The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer Gou, Lan-Ying Li, An-Na Yang, Jin-Ji Zhang, Xu-Chao Su, Jian Yan, Hong-Hong Xie, Zhi Lou, Na-Na Liu, Si-Yang Dong, Zhong-Yi Gao, Hong-Fei Zhou, Qing Zhong, Wen-Zhao Xu, Chong-Rui Wu, Yi-Long Oncotarget Research Paper MET overexpression and the EGFR T790M mutation are both associated with acquired resistance (AR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). We characterized the frequency, underlying molecular mechanisms, and subsequent treatment for AR in MET overexpressing NSCLC patients with or without the T790M mutation. The study participants were 207 patients with advanced NSCLC and AR to EGFR-TKIs. The percentages of MET-, T790M- and MET/T790M-positive patients were 20.3% (42/207), 34.8% (72/207) and 6.8% (14/207), respectively. The disease control rate was 100% (5/5) for five patients with MET overexpression who received EGFR-TKIs plus a MET inhibitor. Among the MET/T790M-positive patients, seven received EGFR-TKIs plus a MET inhibitor and four received a T790M inhibitor, but no response was observed. The median post-progression survival (PPS) was 14.1, 24.5, and 10.7 months for MET-overexpressing, T790M-positive and MET/T790M-positive patients, respectively (P=0.044). c-Met, p-Met, ERBB3, and p-ERBB3 were highly expressed in MET-positive and MET/T790M-positive patients, but were poorly expressed in T790M-positive patients. EGFR, p-EGFR, AKT, p-AKT, MAPK, and p-MAPK were highly expressed in all three groups. These results suggest that MET/T790M-positive patients are at higher risk of AR to EGFR-TKIs, and have a worse PPS than patients with only MET overexpression or the T790M mutation alone. Clinical trials are needed to determine the best treatment for patients with both MET overexpression and the EGFR T790M mutation. Impact Journals LLC 2016-05-30 /pmc/articles/PMC5239477/ /pubmed/27259997 http://dx.doi.org/10.18632/oncotarget.9697 Text en Copyright: © 2016 Gou et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gou, Lan-Ying Li, An-Na Yang, Jin-Ji Zhang, Xu-Chao Su, Jian Yan, Hong-Hong Xie, Zhi Lou, Na-Na Liu, Si-Yang Dong, Zhong-Yi Gao, Hong-Fei Zhou, Qing Zhong, Wen-Zhao Xu, Chong-Rui Wu, Yi-Long The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer |
title | The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer |
title_full | The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer |
title_fullStr | The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer |
title_full_unstemmed | The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer |
title_short | The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer |
title_sort | coexistence of met over-expression and an egfr t790m mutation is related to acquired resistance to egfr tyrosine kinase inhibitors in advanced non-small cell lung cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239477/ https://www.ncbi.nlm.nih.gov/pubmed/27259997 http://dx.doi.org/10.18632/oncotarget.9697 |
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