Src promotes survival and invasion of lung cancers with epidermal growth factor receptor abnormalities and is a potential candidate for molecular-targeted therapy

摘要: Molecular-targeted therapy using tyrosine kinase inhibitors against epidermal growth factor receptor (EGFR) is an effective for non-small cell lung cancer that harbor EGFR mutations. This study aimed to investigate the role of Src, a close associator, as drug target in NSCLC cells with different genomic statuses. Src inhibition was achieved 4-(4'-Phenoxyanilino)-6,7-dimethoxyquinazolinee (SKI-1) and specificity action verified by RNA interference. The results showed SKI-1 induced significant apoptosis dose-dependent manner high basal activation. Activation FAK p130Cas involved Src-mediated invasion SKI-1-sensitive cells. inhibited phosphorylation well downstream effectors, such signal transducers activators transcription 3/5, extracellular signal-regulated 1/2 AKT mutant but not wild-type profile implicates induction sensitivity SKI treatment mediated pathways. Cotreatment gefitinib enhanced contained mutation and/or amplification. alone H1975 known be resistant gefitinib. shown immunohistochemistry around 30% primary carcinomas. In 152 adenocarcinomas studied, p-Src associated mutations (P = 0.029). Overall, findings indicated could useful cancer. Besides mutations, other forms related family member abnormalities amplification might enhance sensitivity.