Drug Discovery and Development Division, Shizuoka Cancer Center, Shizuoka, Japan.
Region Resources Division, Shizuoka Cancer Center, Shizuoka, Japan.
Anticancer Res. 2014 Jun;34(6):2779-87.
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.
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.
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.
Enhanced glutamine metabolism may be a surrogate marker that can be used to predict the likelihood of patients to respond to EGFR-TKIs.
背景/目的：表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）耐药的获得仍然是肺癌治疗中的主要挑战。我们试图确定用于早期检测 TKI 耐药的生物标志物。
采用毛细管电泳飞行时间质谱分析鉴定与 EGFR 突变型非小细胞肺癌细胞系 PC-9 中建立的 EGFR 突变型非小细胞肺癌细胞系 PC-9ER 中厄洛替尼耐药相关的代谢特征。
PC-9ER 细胞表现出增强的谷氨酰胺代谢的代谢特征。还检测到 v-myc 禽髓细胞瘤病毒致癌基因同源物（MYC）、谷胱甘肽-S-转移酶 theta 2（GSTT2）、γ-谷氨酰转移酶 1（GGT1）和 GGT5 的拷贝数增加，表明这些基因的扩增使 PC-9ER 细胞对谷氨酰胺产生依赖。
增强的谷氨酰胺代谢可能是一种替代标志物，可用于预测患者对 EGFR-TKI 反应的可能性。
