1. Identification of metabolic signatures associated with erlotinib resistance of non-small cell lung cancer cells.
- Author
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Serizawa M, Kusuhara M, Zangiacomi V, Urakami K, Watanabe M, Takahashi T, Yamaguchi K, Yamamoto N, and Koh Y
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma genetics, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, DNA Copy Number Variations genetics, Electrophoresis, Capillary, Erlotinib Hydrochloride, Humans, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Polymerase Chain Reaction, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tumor Cells, Cultured, Adenocarcinoma metabolism, Biomarkers, Tumor metabolism, Carcinoma, Non-Small-Cell Lung metabolism, Drug Resistance, Neoplasm, Lung Neoplasms metabolism, Metabolome drug effects, Protein Kinase Inhibitors pharmacology, Quinazolines pharmacology
- Abstract
Background/aim: The acquisition of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remains a major challenge in lung cancer medicine. We sought to identify biomarkers for the early detection of resistance to TKIs., Materials and Methods: Capillary electrophoresis time-of-flight mass spectrometry analysis was performed to identify the metabolic signatures associated with erlotinib resistance in erlotinib-resistant PC-9ER NSCLC cells established from the EGFR-mutant NSCLC cell line PC-9., Results: PC-9ER cells showed metabolic signatures indicative of enhanced glutamine metabolism. Copy number gains in v-myc avian myelocytomatosis viral oncogene homolog (MYC), glutathione-S-transferase theta 2 (GSTT2), gamma-glutamyltransferase 1 (GGT1), and GGT5 were also detected, suggesting that amplification of these genes confers glutamine addiction in PC-9ER cells., Conclusion: Enhanced glutamine metabolism may be a surrogate marker that can be used to predict the likelihood of patients to respond to EGFR-TKIs., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2014