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
| Autor: | Xu-Chao Zhang, Jian Su, Zhi Xie, Hong-Hong Yan, Yi-Long Wu, Hong-Fei Gao, Chong-Rui Xu, Zhong-Yi Dong, Jin-Ji Yang, A. Li, Wen-Zhao Zhong, Si-Yang Liu, Qing Zhou, Lan-Ying Gou, Na-Na Lou |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Threonine 0301 basic medicine Oncology MAPK/ERK pathway medicine.medical_specialty Lung Neoplasms Mutation Missense medicine.disease_cause T790M Young Adult 03 medical and health sciences Methionine 0302 clinical medicine Acquired resistance EGFR-TKI Carcinoma Non-Small-Cell Lung Internal medicine medicine Humans ERBB3 Lung cancer Protein Kinase Inhibitors Protein kinase B non-small cell lung cancer Aged Mutation business.industry acquired resistance Middle Aged Proto-Oncogene Proteins c-met medicine.disease Up-Regulation respiratory tract diseases ErbB Receptors Gene Expression Regulation Neoplastic Clinical trial 030104 developmental biology Amino Acid Substitution Drug Resistance Neoplasm 030220 oncology & carcinogenesis MET Disease Progression Female business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.9697 |
| Popis: | // Lan-Ying Gou 1, 2, * , An-Na Li 2, * , Jin-Ji Yang 2, * , Xu-Chao Zhang 2 , Jian Su 2 , Hong-Hong Yan 2 , Zhi Xie 2 , Na-Na Lou 2 , Si-Yang Liu 2 , Zhong-Yi Dong 2 , Hong-Fei Gao 2 , Qing Zhou 2 , Wen-Zhao Zhong 2 , Chong-Rui Xu 2 , Yi-Long Wu 2 1 Southern Medical University, Guangzhou, Guangdong, People’s Republic of China 2 Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Yi-Long Wu email: syylwu@live.cn Keywords: non-small cell lung cancer, EGFR-TKI, acquired resistance, MET, T790M Received: March 19, 2016 Accepted: May 13, 2016 Published: May 30, 2016 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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