Document Detail


Combined Erlotinib and Cetuximab overcome the acquired resistance to epidermal growth factor receptors tyrosine kinase inhibitor in non-small-cell lung cancer.
MedLine Citation:
PMID:  22821179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Non-small-cell lung cancer (NSCLC) cells with somatic mutations in epidermal growth factor receptors (EGFR) are initially susceptible to tyrosine kinase inhibitor (TKI); however, eventually resistance to TKI is developed in these cells, which leads to the failure of treatment. The most common mechanism of this acquired drug resistance is development of a secondary T790M mutation in EGFR. In this study, we investigated the effects of the combination of Erlotinib and Cetuximab on T790M and L858R mutation lung cancer cells lines (H1975), in the primary NSCLC cells with the T790M mutation and TKI-resistant EGFR mutations human tumor xenograft model (H1975).
METHODS: The effects of these two agents on cell proliferation, apoptosis, and EGFR-dependent signaling were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V staining, and Western blotting. Sensitivity of EGFR inhibitors was detected in the primary tumor cell suspension and human tumor xenograft model (H1975).
RESULTS: Compared with single-agent treatment, the combination of Cetuximab and Erlotinib increased apoptosis of EGFR TKI-resistant NSCLC cells (H1975), resulting in more pronounced growth inhibition on cell proliferation and significant inhibition of EGFR-dependent signaling.
CONCLUSIONS: These data suggest that treatment with a combination of Erlotinib and Cetuximab overcomes T790M-mediated drug resistance.
Authors:
Meng Wang; Jing Zhao; Lian-Min Zhang; Hui Li; Jin-Pu Yu; Xiu-Bao Ren; Chang-Li Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-22
Journal Detail:
Title:  Journal of cancer research and clinical oncology     Volume:  138     ISSN:  1432-1335     ISO Abbreviation:  J. Cancer Res. Clin. Oncol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-07     Completed Date:  2013-04-01     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7902060     Medline TA:  J Cancer Res Clin Oncol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2069-77     Citation Subset:  IM    
Affiliation:
Key Laboratory of Cancer Prevention and Therapy Tianjin, Department of Lung Cancer, Cancer Institute & Hospital, Tianjin Medical University, Tianjin, 300060, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects,  genetics
Carcinoma, Non-Small-Cell Lung / drug therapy*,  enzymology,  genetics,  metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Resistance, Neoplasm
Female
Humans
Lung Neoplasms / drug therapy*,  enzymology,  genetics,  metabolism
Mice
Mice, Nude
Mutation / drug effects
Protein Kinase Inhibitors / pharmacology*
Protein-Tyrosine Kinases / antagonists & inhibitors*
Quinazolines / administration & dosage
Receptor, Epidermal Growth Factor / genetics,  metabolism*
Signal Transduction / drug effects,  genetics
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Protein Kinase Inhibitors; 0/Quinazolines; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, Epidermal Growth Factor; J4T82NDH7E/erlotinib; PQX0D8J21J/cetuximab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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