Project description:The aim of the study was to characterize the gene expression profiles of PC9 cells exposed to sorafenib and osimertinib, alone or in combination. PC9 cells were cultured in presence of sorafenib and osimertinib for 1day, 2 days and 4 days. Genome-wide expression profiling (Agilent microarrays) were used to characterize the transcriptome of PC9 cells and to identify specific gene exptression signatures and functionally relevant gene networks linked to sorafenib and osimertinib treatments.
Project description:To investigate the possible resistant mechanism to osimertinib, PC9 cells and their derived osimertinib-resistant PC9OR cells were sequenced using illumina HiSeq. We then performed gene expression profiling analysis using data obtained from RNA-seq of PC9 cells and their derived PC9OR cells.
Project description:The experiment investigates transcriptional reponse of EGFR-mut PC9 lung cancer cells following treatment for 24h or 72h with EGFR-inhibitor osimertinib compared to control cells on a single cell level.
Project description:Human EGFR-mutant lung adenocarcinoma cells (PC9) were engineered using CRISPRv2 systemt to knock-out MAVS or STING to assess impact on transcriptomic response following osimertinib treatment
Project description:To investigate the abnormal gene expression in Osimertinib Resistance lung cancer cell line, We performed gene expression profiling analysis using data obtained from RNA-seq of PC9 cell line and PC9-OR cell line.
Project description:Immunocompromised mice were inoculated with human lung adenocarcinoma cell line PC9 and with human PBMCs. Tumors were treated with osimertinib/vehicle of RIG-I agonist IVT4/unspecific control IVT-GAC to assess response.
Project description:Targeting drug tolerant persister (DTP) cells may present a therapeutic opportunity to eliminate residual surviving tumor cells and impede relapse. We sought to identify therapeutically exploitable vulnerabilities in DTP cells using the EGFR-mutant non-small cell lung cancer cell line PC9 as an experimental model. Here we provide RNAseq gene expression profiling data generated from parental PC9 cells compared to PC9 DTP cells generated from nine days of treatment with 2 uM osimertinib. These data can be used to identify genes and pathways which are upregulated in DTP cells, revealing potential therapeutic targets.
Project description:Drug tolorent persister cells induced by target therapy are marked by elevated level of compressed chromatin structure. We use ChIP seq against H3K27me3 or H3K9me3 antibody to reveal the repressive chromatin regions of osimertinib-treated PC9 cells.
Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. Using PC9 cells, we generated EGFR-mutant lung cancer xenografts to study the differences in response between individual cells and cell populations. We performed treatment of PC9 xenograft tumors with the combination of osimertinib and crizotinib as well as single drugs, followed by Drop-seq. The addition of crizotinib was guided by our previous data in PC9 grown in cell culture that identified an erlotinib-resistant drug population sensitive to crizotinib. The results of the xenograft study show that combination treatment targets specific osimertinib-tolerant cell populations but leaves a subset of the population that is tolerant to the combo. Each cell subpopulation is characterized by specific molecular signatures. The results of our study help to address emerging drug resistance that limits clinical usefulness of targeted strategies, particularly in NSCLC.
Project description:Sorafenib is associated with cardiac adverse effects, including left ventricular dysfunction. However, the precise mechanism remains unclear. Here, we aimed to establish the genes responsible for this cardiotoxicity using zebrafish. A pigmentless zebrafish line expressing green fluorescent protein in the heart were treated with or without sorafenib. In vivo fluorescent cardiac imaging revealed that the ventricular dimension of the longitudinal axis in zebrafish treated with sorafenib was significantly lower than in those without sorafenib. Transcriptome analysis of zebrafish hearts revealed that expression of stanniocalcin1 (stc1) in zebrafish treated with sorafenib was significantly lower than that without sorafenib treatment. We were able to demonstrate that the ventricular dimension of the longitudinal axis in stc1 morphant was significantly smaller than that of control zebrafish and that forced expression of stc1 normalized the decrease in ventricular diameter in stc1 morphant and zebrafish treated with sorafenib. These data suggest that stc1 is the gene responsible for sorafenib-induced cardiotoxicity. Gene expression regulated by sorafenib in zebrafish at 4 dpf was measured. Four independent experiments were performed for each group.