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The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [ChIP-seq]

ABSTRACT: The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [ChIP-seq]

PROVIDER: PRJNA795500 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17489747.fastq.gz	Fastqsanger.gz
	SRR17489748.fastq.gz	Fastqsanger.gz
	SRR17489749.fastq.gz	Fastqsanger.gz
	SRR17489750.fastq.gz	Fastqsanger.gz
	SRR17489751.fastq.gz	Fastqsanger.gz

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The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [ChIP-seq]

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.

2022-04-06 | GSE193257 | GEO

The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [RNA-seq]

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The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [ATAC-seq]

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The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells

Project description:The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells

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The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [ATAC-seq]

Project description:The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [ATAC-seq]

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The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [RNA-seq]

Project description:The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [RNA-seq]

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Drug tolerant persister cells of EGFR-mutant cell line under kinase-inhibitor combination

Project description:Drug tolerant persister cells of EGFR-mutant PC9 cell lines surviving treatment with kinase inhibitor combination. Cells were treated with combination of erlotinib, osimertinib, trametinib and dasatinib and surviving cells were harvested for RNA extraction. 3' UTR RNA-seq profiles were compared to parental control cells and to outgrowing cells after treatment had been removed

2023-06-30 | E-MTAB-13045 | biostudies-arrayexpress

Gene expression profiling of drug-tolerant persister PC9 non-small cell lung cancer cells derived from osimertinib treatment

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.

2020-06-25 | GSE153183 | GEO

Expression data of osimertinib tolerant H1975 cells

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.

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Eradicating Drug Tolerant Persister Cells in EGFR-Mutated Non-Small Cell Lung Cancer by Targeting TROP2 with CAR-T cellular therapy

Project description:EGFR tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes for EGFR-mutated non-small cell lung cancer (NSCLC) patients, but relapse frequently occurs due to drug tolerant persister (DTP) cells that can evolve and develop diverse mechanisms of drug resistance. In samples from patients with EGFR-mutated NSCLC treated with an EGFR-TKIs in the neoadjuvant setting, we observed uniformly elevated expression of the cell surface protein TROP2, a target of clinically active antibody drug conjugates (ADCs). We further confirmed that TROP2 expression is enriched in DTPs following osimertinib treatment of EGFR-mutated NSCLC cell lines and xenograft models. At the time of osimertinib-induced minimal residual disease, treatment with TROP2 ADC sacituzumab govitecan had only a modest impact on delaying tumor recurrence in vivo. In contrast, a single treatment of TROP2 directed CAR-T treatment significantly prolonged relapse-free survival with evidence of cure, highlighting the ability of CAR-T therapy to eliminate DTPs in vivo.

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