Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ABCB1 amplification drives paclitaxel resistance in PDAC cells, which can be targeted by novel drug combination strategies

ABSTRACT: ABCB1 amplification drives paclitaxel resistance in PDAC cells, which can be targeted by novel drug combination strategies

PROVIDER: PRJNA948044 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23950453_1.fastq.gz	Fastqsanger.gz
	SRR23950453_2.fastq.gz	Fastqsanger.gz
	SRR23950454_1.fastq.gz	Fastqsanger.gz
	SRR23950454_2.fastq.gz	Fastqsanger.gz
	SRR23950455_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

ABCB1 amplification drives paclitaxel resistance in PDAC cells, which can be targeted by novel drug combination strategies

Project description:This study investigate PDAC resistance to paclitaxel.

2024-01-10 | GSE228106 | GEO

Human Pancreatic Ductal Adenocarcinoma (PDAC), LC-MS/MS

Project description:The aim of the study was to characterize a common molecular mechanism for paclitaxel resistance in Patu-T and Suit-2.028 PDAC cell lines. Despite the ATP-binding cassette (ABC) trasnsporters were already shown to be involved in various chemo-resistant forms of cancers but not in PDAC, the most likely impact of ABCB1 overexpression in PDAC cell models was taken into account in this dataset.

2024-01-26 | PXD040930 | Pride

Gene expression profiling of ABCB1 positive and ABCB1 negative OCM1A cells

Project description:Gene expression profiling of ABCB1 positive and ABCB1 negative OCM1A cells. ABCB1 is an ATP-dependent transporter efflux pump. OCM1A cell line is derived from uveal melanomas. 6 samples (3 ABCB1 positive and 3 ABCB1 negative) from 3 independent ABCB1 shift assays were analysed

2010-09-01 | E-GEOD-21425 | biostudies-arrayexpress

c-Myc drives nab-paclitaxel resistance in pancreatic cancer

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and very often, ineffective medical and surgical therapeutic options. The treatment of patients with advanced unresectable PDAC is restricted to systemic chemotherapy, a therapeutic intervention to which most eventually develop resistance. Recently, nab-paclitaxel has been added to the arsenal of first line therapies, and the combination of gemcitabine and nab-paclitaxel has modestly prolonged median overall survival. However, patients almost invariably succumb to the disease, and little is known about the mechanisms underlying nab-paclitaxel (n-PTX) resistance. Using the conditionally reprogrammed (CR) cell approach, we established and verified continuously growing cell cultures from treatment-naive PDAC patients. To study the mechanisms of primary drug resistance, nab-paclitaxel-resistant (n-PTX-R) cells were generated from primary cultures and drug resistance was verified in vivo, both in zebrafish and in athymic nude mouse xenograft models. Molecular analyses identified the sustained induction of c-MYC in the nab-paclitaxel-resistant cells. Depletion of c-Myc restored nab-paclitaxel sensitivity, as did treatment with either the MEK inhibitor, trametinib, or a small molecule activator of protein phosphatase 2a (SMAP). Implications: The strategies we have devised, including the patient-derived primary cells and the unique drug resistant isogenic cells, are rapid and easily applied in vitro and in vivo platforms to better understand the mechanisms of drug resistance and for defining effective therapeutic options on a patient by patient basis

2019-05-31 | GSE131762 | GEO

Gene expression profiling of ABCB1 positive and ABCB1 negative OCM1A cells

Project description:Gene expression profiling of ABCB1 positive and ABCB1 negative OCM1A cells. ABCB1 is an ATP-dependent transporter efflux pump. OCM1A cell line is derived from uveal melanomas.

2010-09-01 | GSE21425 | GEO

ecDNA amplification of MYC drives intratumor copy-number heterogeneity and adaptation to stress in PDAC

Project description:Intratumor heterogeneity and phenotypic plasticity drive tumour progression and therapy resistance. Oncogene dosage variation contributes to cell state transitions and phenotypic heterogeneity, thereby providing a substrate for somatic evolution. Nonetheless, the genetic mechanisms underlying phenotypic heterogeneity are still poorly understood. Here, we show that extrachromosomal DNA (ecDNA) is a major source of high-level focal amplification in key oncogenes and a major contributor of MYC heterogeneity in pancreatic ductal adenocarcinoma (PDAC). We demonstrate that ecDNAs drive varying levels of MYC dosage, depending on their regulatory landscape, enabling cancer cells to rapidly and reversibly adapt to microenvironmental changes. In absence of selective pressure, a high ecDNA copy number imposes a substantial fitness cost on PDAC cells. We also show that MYC dosage affects cell morphology and dependence of cancer cells on stromal niche factors. Our work provides the first detailed analysis of ecDNAs in PDAC and describes a new genetic mechanism driving MYC heterogeneity in PDAC.

2024-12-29 | GSE247129 | GEO

Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma

Project description:Aberrant tyrosine kinase activity can influence tumor growth and is regulated by phosphorylation. Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. We investigated phosphorylated kinases as target in PDAC. Mass spectrometry-based phosphoproteomic analysis was performed of PDAC cell lines to evaluate active kinases. Pathway analysis and inferred kinase activity was performed to identify novel targets. We investigated targeting of focal adhesion kinase in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Phosphoproteome analysis upon treatment was performed to evaluate signaling..PDAC cell lines portrayed high activity of multiple receptor tyrosine kinases. Non-receptor kinase, focal adhesion kinase (FAK), was identified in all cell lines by our phosphoproteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo. In conclusion, our study shows a high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel

2021-09-10 | PXD024548 | Pride

Transcriptome profiles of antibody-producing CHO cells across different amplification strategies

Project description:Transcriptome profiles of antibody-producing CHO cells across different amplification strategies

| PRJNA551666 | ENA

Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET inhibitor in Non-Small Cell Lung Cancer

Project description:Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitor. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC1 cells, namely EBC1-R cells. EBC1-R cells showed overexpression of ATP-binding cassette sub-family B member 1 (ABCB1) as well as phosphorylation of MET. EBC1-R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial mesenchymal transition (EMT). The levels of two miRNAs, miR-374a and miR-138 which targeted ABCB1, were decreased in EBC1-R cells. ABCB1 siRNA and ABCB1 inhibitor elacridar could reduce sphere numbers and suppress EMT. Elacridar could also reverse the resistance to PHA-665752 in EBC1-R cells. Our study demonstrated that ABCB1 overexpression which was associated with CSC properties and EMT was involved in the acquired resistance to MET inhibitor. Inhibition of ABCB1 might be a novel therapeutic strategy for NSCLC patients with acquired resistance to MET inhibitor.

2015-03-07 | GSE66604 | GEO