Elevated neutrophil gelatinase-associated lipocalin contributes to erlotinib resistance in non-small cell lung cancer.

摘要: Purpose: The EGFR tyrosine kinase inhibitors (TKIs) demonstrate efficacy in NSCLC patients whose tumors harbor activating mutations. However, who initially respond to TKI treatment invariably develop resistance the drugs. Known mechanisms account for approximately 70% of native and acquired resistance. In current study we investigated a novel mechanism erlotinib. Experimental Design: erlotinib were evaluated by microarray analysis thirteen cell lines vivo mice. Correlations between plasma neutrophil gelatinase associated lipocalin (NGAL) levels, response mutational status assessed advanced stage treated with Results: 5 13 NGAL was significantly upregulated. knockdown erlotinib-resistant cells increased sensitivity vitro vivo. overexpression erlotinib-sensitive augmented apoptosis This mediated NGAL-dependent modulation pro-apoptotic protein Bim levels. Evaluation levels that received revealed lower baseline demonstrated better response. Compared wild type EGFR, mutations had at weeks 4 8. Conclusions: Our studies uncover NGAL-mediated might contribute lung cancer patients. These findings provide rationale further investigations utility as potential therapeutic target or diagnostic biomarker.