作者: Christine A. Pratilas , Aphrothiti J. Hanrahan , Ensar Halilovic , Yogindra Persaud , Junichi Soh
DOI: 10.1158/0008-5472.CAN-08-2223
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摘要: Hyperactivated extracellular signal-regulated kinase (ERK) signaling is common in human cancer and often the result of activating mutations BRAF, RAS, upstream receptor tyrosine kinases. To characterize mitogen-activated protein kinase/ERK (MEK)/ERK dependence lung cancers harboring BRAF domain mutations, we screened a large panel cell lines (n = 87) tumors 916) for mutations. We found that non-small (NSCLC) cells with both V600E non-V600E were selectively sensitive to MEK inhibition compared those epidermal growth factor (EGFR), KRAS, or ALK ROS fusions. Supporting its classification as "driver" mutation which it expressed, (V600E)BRAF NSCLC led substantial induction apoptosis, comparable seen EGFR mutant models. Despite high basal ERK phosphorylation, uniformly resistant inhibition. Conversely, These data, together nonoverlapping pattern cancer, suggest these lesions define distinct clinical entities whose treatment should be guided by prospective real-time genotyping. facilitate such an effort, developed mass spectrometry-based genotyping method detection hotspot EGFR. Using this assay, confirmed can identified minority patients harbor have profile