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:Osimertinib, a third-generation EGFR-TKI, has applied to non-small cell lung cancer harboring activated EGFR mutation with or without T790M. However, the appearance of tumors resistant to osimertinib has been reported. We established and characterized osimertinib-resistant cells derived from NCI-H1975 cells harboring activating EGFR and T790M mutation.
Project description:The H1975 osimertinib resistant (H1975 OR) cell lines were successfully established by subjecting parental H1975 cells to a gradually increasing concentration of osimertinib up to 1μM for a duration exceeding 2 months. In order to investigate the molecular alterations associated with osimertinib resistance, we analyzed the transcriptional profiling of parental H1975 cells and H1975 OR cells by RNA sequencing.
Project description:To tentatively explored the latent roles of miRNAs in Osimertinib treatment response and tried to explore the methylation related miRNA maturation in the generation of resistance
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: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.