title: Identification of metabolic signatures associated with erlotinib resistance of non-small cell lung cancer cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Enhanced glutamine metabolism may be a surrogate marker that can be used to predict the likelihood of patients to respond to EGFR-TKIs.
authors.affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.affiliation: Region Resources Division, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
authors.affiliation: Region Resources Division, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zangiacomi
authors.affiliation: Cancer Diagnostics Research Division, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Urakami
authors.affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Region Resources Division, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center, Shizuoka, Japan y.koh@scchr.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D056915:DNA Copy Number Variations / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D019075:Electrophoresis, Capillary; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D055442:Metabolome / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride
keywords: EGFR-TKI resistance; MYC; copy-number alteration; glutamine metabolism; metabolomics; non-small cell lung cancer