Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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
_version_ 1782495902194204672
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
work_keys_str_mv AT goulanying thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT lianna thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT yangjinji thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT zhangxuchao thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT sujian thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT yanhonghong thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT xiezhi thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT lounana thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT liusiyang thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT dongzhongyi thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT gaohongfei thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT zhouqing thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT zhongwenzhao thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT xuchongrui thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT wuyilong thecoexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT goulanying coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT lianna coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT yangjinji coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT zhangxuchao coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT sujian coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT yanhonghong coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT xiezhi coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT lounana coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT liusiyang coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT dongzhongyi coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT gaohongfei coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT zhouqing coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT zhongwenzhao coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT xuchongrui coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer
AT wuyilong coexistenceofmetoverexpressionandanegfrt790mmutationisrelatedtoacquiredresistancetoegfrtyrosinekinaseinhibitorsinadvancednonsmallcelllungcancer