Hcc78_crizo
Ontology highlight
ABSTRACT:
TISSUE(S): Lung
DISEASE(S): Infected With Hbv Xmutant
SUBMITTER: liangliang,cai
REPOSITORIES: NODE
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Project description:The non-small cell lung cancer (NSCLC) cell line HCC827 harbors an activating EGFR mutation (exon 19 deletion) that confers sensitivity to the FDA-approved EGFR inhibitor erlotinib. By applying the ClonTracer barcoding system, we were able to show the presence of pre-existing sub-populations in HCC827 that contribute to erlotinib resistance. Prior studies implicated that MET amplification confers resistance to erlotinib in this cell line. Therefore we examined the effects of the c-Met inhibitor crizotinib on the barcoded HCC827 population when treated either sequentially or simultaneously with both inhibitors. Despite the significant reduction in barcode complexity, the erlotinib/crizotinib combination treatment failed to eradicate all of the resistant clones implying the presence of an erlotinib/crizotinib dual resistant subpopulation. We performed transcriptome profiling (RNA-seq) to elucidate the potential resistance mechanisms of the dual resistant subpopulation in comparison to vehicle-treated or single agent erlotinib-resistant HCC827 cell populations as controls.
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