Project description:We have employed a transcriptomic approach to find a molecular target that could compensate for the loss of EGFR signaling in NSCLC cell lines with acquired resistance to gefitinib with an EMT phenotype.
Project description:To identify novel miRNAs involved in acquired EGFR TKI resistance in NSCLC, genome-wide miRNA expression analysis was performed in gefitinib-resistant sub-cell lines and gefitinib-sensitive parental cell lines.
Project description:The Epidermal Growth Factor Receptor (EGFR) regulates a diverse set of biological processes including cell growth, proliferation, and differentiation. Deregulation of the EGFR pathway has been implicated in a variety of human diseases including cancer. Gefitinib and erlotinib are tyrosine kinase inhibitors (TKIs) that have demonstrated clinical benefit for patients with Non-small cell lung cancer (NSCLC) and EGFR activating mutations. However, patients invariably acquire resistance to TKI treatment through a number of mechanisms. We utilized in vitro models of NSCLC with EGFR activating mutations and derived three isogenic cell lines with acquired resistance to gefitinib. We next studied genomewide mRNA expression in resistance and wild type cells and their effect in the reprogramming of pathways in lung cancer cell line models..
Project description:The Epidermal Growth Factor Receptor (EGFR) regulates a diverse set of biological processes including cell growth, proliferation, and differentiation. Deregulation of the EGFR pathway has been implicated in a variety of human diseases including cancer. Gefitinib and erlotinib are tyrosine kinase inhibitors (TKIs) that have demonstrated clinical benefit for patients with Non-small cell lung cancer (NSCLC) and EGFR activating mutations. However, patients invariably acquire resistance to TKI treatment through a number of mechanisms. We utilized in vitro models of NSCLC with EGFR activating mutations and derived three isogenic cell lines with acquired resistance to gefitinib. We next studied genomewide mRNA expression in resistance and wild type cells and their effect in the reprogramming of pathways in lung cancer cell line models..
Project description:About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI. We used microarray to look at global gene expression changes in untreated cells vs gefitinib treated cells to identify key characters for the acquisition of resistance. NSCLC cells, H322c, were cultured 4 days in media containing 1?M gefitinib or 0.1% DMSO as a control. On day 4, RNA was extracted and submitted for microarray hybridization.
Project description:In order to analyze the molecular effect of the combination of Notch inhibitors and EGFR inhibitors on resistance to TKI, we performed RNA-seq gene expression profiling of PC9 resistant to Gefitinib cells treated with different combinations.
Project description:In this study, we explored the mechanisms of hypoxia-induced EGFR TKI resistance in non-small cell lung cancer (NSCLC) harbored activating EGFR mutation. The NSCLC cell lines were exposed to normorxia or 1% oxygen for 4 weeks, and then we tested EGFR TKI sensitivity in normoxic and hypoxic NSCLC cell lines. In this microarray experiment, we used normoxic HCC827 and hypoxia-induced gefitinib resistant clones, C2-3 and C2-10. Those clones were selected with gefitinib treatment after the HCC827 were exposed to 1% oxygen for 4 weeks, and the HCC827 C2-3 and C2-10 clones were selected at random for this study.
Project description:About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI. We used microarray to look at global gene expression changes in untreated cells vs gefitinib treated cells to identify key characters for the acquisition of resistance.
Project description:Analysis of gefitinib short-term resistance at gene expression level. The hyposthesis tested in the present study was that short-term resistance towards gefitinib in NSCLC cells influences pathways that associates with resistance towards EGFR-TKI treatment. Results provide important information of the response of EGFR mutant NSCLC cells to gefitinib and also to resistance towards gefitinib resistance, up-or down-regulated specific resistance pathways and cellular functions.