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Drug holiday expression profiling of non-small cell lung carcinoma cell line PC9 treated with erlotinib

ABSTRACT: Drug holiday expression profiling of non-small cell lung carcinoma cell line PC9 treated with erlotinib

PROVIDER: PRJNA556613 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11596857_1.fastq.gz	Fastqsanger.gz
	SRR11596857_2.fastq.gz	Fastqsanger.gz
	SRR9833133_1.fastq.gz	Fastqsanger.gz
	SRR9833133_2.fastq.gz	Fastqsanger.gz
	SRR9833134_1.fastq.gz	Fastqsanger.gz

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Drug holiday expression profiling of non-small cell lung carcinoma cell line PC9 treated with erlotinib

Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. To be able to better understand the differences in response between individual cells to drug removal after continuous treatment, we performed treatment of PC9 cells grown in cell culture with erlotinib followed by Drop-seq. We were able to clearly distinguish cells that were treated with the drug, removed from the drug and then re-treated with the same drug, and we discovered different cell populations within the treated cells, likely reflecting heterogeneity of drug resistant cells. We were able to identify specific biomarkers, as preferentially expressed genes, for each cell population. The results of our study will address drug resistance that limits clinical usefulness of targeted strategies, particularly in NSCLC.

2020-12-19 | GSE134841 | GEO

Profiling non-small cell lung carcinoma cell line PC9 treated with erlotinib

Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. To be able to better understand the differences in response between individual cells, we performed treatment of PC9 cells grown in cell culture with erlotinib followed by Drop-seq. We were able to clearly distinguish cells that were treated with the drug for five different time points from untreated cells, and we discovered different cell populations within the treated cells, likely reflecting heterogeneity of drug resistant cells. We were able to identify specific biomarkers, as preferentially expressed genes, for each cell population. The results of our study will address preexisting and acquired drug resistance that limits clinical usefulness of targeted strategies, particularly in NSCLC.

2020-12-19 | GSE134839 | GEO

Profiling non-small cell lung carcinoma cell line PC9 treated with etoposide, erlotinib and its combination with crizotinib

Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. To be able to better understand the differences in response between individual cells, we performed treatment of PC9 cells grown in cell culture with etoposide, erlotinib and its combination with crizotinib, followed by Drop-seq. The addition of crizotinib was guided by our previous data that an erlotinib-resistant drug population may be sensitive to crizotinib. To better understand the common events in drug resistance, we compared the resistant cell populations arising from the treatment with etoposide and from the treatment with erlotinib. The results of our study will address emerging drug resistance that limits clinical usefulness of conventional and targeted strategies, particularly in NSCLC.

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Profiling non-small cell lung carcinoma cell line PC9 treated with erlotinib using 10x Genomics

Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. To be able to better understand the differences in response between individual cells, we performed treatment of PC9 cells grown in cell culture with erlotinib followed by 10x Genomics. We were able to clearly distinguish cells that were treated with the drug from untreated cells, and we discovered different cell populations within the treated cells, likely reflecting heterogeneity of drug resistant cells. We were able to identify specific biomarkers, as preferentially expressed genes, for each cell population. The results of our study will address preexisting and acquired drug resistance that limits clinical usefulness of targeted strategies, particularly in NSCLC.

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RNA sequencing of PC9 and four erlotinib-persister cells derived from PC9

Project description:Given the recent reports on the role of AXL in mediating resistance to EGFR-targeted therapy, we generated cell line models of Erlotinib-resistance to investigate the effect of AXL inhibitors on EGFR TKI resistance. For this, EGFR-mutant PC9 cells were passed through a persister bottleneck by applying strong drug selection pressure to generate drug-tolerant erlotinib persister cells. We created four Erlotinib-resistant clones from one parental population; S1-34, S2-10, S2-17 and S2-30. Whole exome and RNA sequencing analyses were performed to probe the differences in Erlotinib-resistance mechanisms present in these persister-derived Erlotinib-resistant cells.

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Gene expression profiling of erlotinib-resistant PC9 cells.

Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. To better understand gene expression changes in cells that survived the inhibitor treatment, we treated the EGFR-mutant PC9 cells with erlotinib, isolated RNA, and performed RNA-seq analysis. We were able to identify genes that are differentially expressed in erlotinib-treated cells compared to untreated. The results of this study will be integrated with single cell RNA-seq to address the utility of bulk RNA versus single cell RNA strategies in identifying biomarkers of drug resistance.

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Profiling non-small cell lung carcinoma cell line PC9 treated with erlotinib, KDM5A inhibitor, or viruses expressing KDM5 shRNAs or cDNA

Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. Recent evidence suggests that KDM5A protein is required for emerging drug-resistant cell population. To better understand the dependence of cell survival on KDM5A, we treated EGFR-mutant PC9 cells with erlotinib, KDM5A inhibitor or KDM5A and KDM5B shRNAs and performed Drop-seq. We were able to clearly distinguish cells with KDM5A knockdown from cells with KDM5A overexpression. We were able to identify specific biomarkers associated with varying dose of KDM5A, for each cell population. The results of this study will address clinical usefulness of KDM5A-targeted strategies in overcoming drug resistance, particularly in NSCLC.

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Single cell RNA-seq profiling of erlotinib-resistant PC9 cells

Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. To be able to better understand the differences in response between individual cells, we performed treatment of PC9 cells grown in cell culture with erlotinib followed by Drop-seq. We were able to clearly distinguish cells that were treated with the drug for 11 days from untreated cells, and we discovered different cell populations within the treated cells, likely reflecting heterogeneity of drug resistant cells. We were able to identify specific biomarkers, as preferentially expressed genes, for each cell population. The results of our study will address preexisting and acquired drug resistance that limits clinical usefulness of targeted strategies, particularly in NSCLC.

2020-12-19 | GSE149214 | GEO

Genome-wide map of H3K4me3 in erlotinib-resistant PC9 cells.

Project description:The non-small cell lung carcinoma (NSCLC) PC9 cell line is an established preclinical model for tyrosine kinase inhibitors. Recent evidence suggests that the H3K4 demethylase KDM5A protein is required for emerging drug-resistant cell populations. To better understand the dependence of cell survival on H3K4me3 level, we treated the EGFR-mutant PC9 cells with erlotinib and performed ChIP-seq analysis using H3K4me3 antibodies. We were able to identify genomic regions that exhibit decreased H3K4me3 in drug-treated cells. The results of this study will help to address clinical usefulness of KDM5A-targeted strategies in overcoming drug resistance, particularly in NSCLC.

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Profiling non-small cell lung carcinoma cell line PC9 treated with erlotinib

Project description:Profiling non-small cell lung carcinoma cell line PC9 treated with erlotinib

| PRJNA556612 | ENA