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.
Keywords: EGFR-TKI resistance; MYC; copy-number alteration; glutamine metabolism; metabolomics; non-small cell lung cancer.
Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.