Project description:Even after osimertinib is administered to lung adenocarcinomas with EGFR mutations, there are a few cells which survive, and these tolerant cells are considered to be the source of later recurrence. We used microarray analysis to explore the mechanism behind the tolerance to osimertinib in lung adenocarcinoma cells with EGFR mutations.
Project description:Even after osimertinib is administered to lung adenocarcinomas with EGFR mutations, there are a few cells which survive, and these tolerant cells are considered to be the source of later recurrence. We used microarray analysis to explore the mechanism behind the tolerance to osimertinib in lung adenocarcinoma cells with EGFR mutations.
Project description:Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, an irreversible EGFR-TKI, are important treatments for non-small cell lung cancer with EGFR-TKI sensitizing or EGFR T790M resistance mutations. Whilst patients treated with osimertinib show clinical benefit, disease progression and drug resistance are common. Emergence of de novo acquired resistance from a drug tolerant persister (DTP) cell population is one mechanism proposed to explain progression on osimertinib and other targeted cancer therapies. Here we profiled osimertinib DTPs using RNA-seq, ChIP-seq, and ATAC-seq to characterize the features of these cells and performed drug screens to identify therapeutic opportunities.
Project description:Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, an irreversible EGFR-TKI, are important treatments for non-small cell lung cancer with EGFR-TKI sensitizing or EGFR T790M resistance mutations. Whilst patients treated with osimertinib show clinical benefit, disease progression and drug resistance are common. Emergence of de novo acquired resistance from a drug tolerant persister (DTP) cell population is one mechanism proposed to explain progression on osimertinib and other targeted cancer therapies. Here we profiled osimertinib DTPs using RNA-seq, ChIP-seq, and ATAC-seq to characterize the features of these cells and performed drug screens to identify therapeutic opportunities.
Project description:Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, an irreversible EGFR-TKI, are important treatments for non-small cell lung cancer with EGFR-TKI sensitizing or EGFR T790M resistance mutations. Whilst patients treated with osimertinib show clinical benefit, disease progression and drug resistance are common. Emergence of de novo acquired resistance from a drug tolerant persister (DTP) cell population is one mechanism proposed to explain progression on osimertinib and other targeted cancer therapies. Here we profiled osimertinib DTPs using RNA-seq, ChIP-seq, and ATAC-seq to characterize the features of these cells and performed drug screens to identify therapeutic opportunities.
Project description:Even after osimertinib is administered to lung adenocarcinomas with EGFR mutations, there are a few cells which survive, and these tolerant cells are considered to be the source of later recurrence. We suspect that PAI-1 is involved in the regulation of these resistant cells and are currently investigating the role of PAI-1 in this process. We used microarray analysis to explore mechanisms involving PAI-1 behind the tolerance to osimertinib in lung adenocarcinoma cells with EGFR mutations.
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:Experiment was designed to study the effect of Hippo pathway on osimertinib resistance in non-small cell lung cancer cell lines. The specific comparisons investigated were: PC-9: NTC vs NF2 KO, EV vs YAP1 OE, EV vs WWTR1 OE, EV DMSO treated vs EV osimertinib treated HCC827: NTC vs NF2 KO, EV vs YAP1 OE, EV vs WWTR1 OE,EV DMSO treated vs EV osimertinib treated HCC4006: NTC vs NF2 KO, EV vs YAP1 OE, EV vs WWTR1 OE, EV DMSO treated vs EV osimertinib treated
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.