Masakuni Serizawa1, Masatoshi Kusuhara2, Vincent Zangiacomi2, Kenichi Urakami3, Masaru Watanabe1, Toshiaki Takahashi4, Ken Yamaguchi2, Nobuyuki Yamamoto5, Yasuhiro Koh6. 1. Drug Discovery and Development Division, Shizuoka Cancer Center, Shizuoka, Japan. 2. Region Resources Division, Shizuoka Cancer Center, Shizuoka, Japan. 3. Cancer Diagnostics Research Division, Shizuoka Cancer Center, Shizuoka, Japan. 4. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 5. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. 6. Drug Discovery and Development Division, Shizuoka Cancer Center, Shizuoka, Japan y.koh@scchr.jp.
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
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