JUN-Mediated downregulation of EGFR signaling is associated with resistance to gefitinib in EGFR-mutant NSCLC cell lines [RNA-seq]

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.. Overall design: Differntial expresssion profile of transcripts of parental (HCC827) and EGFR-TKI (HCC827 ZDR3) resistance cells

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Kani K, Garri C, Tiemann K, Malihi PD, Punj V, Nguyen AL, Lee J, Hughes LD, Alvarez RM, Wood DM, Joo AY, Katz JE, Agus DB, Mallick P