Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A whole-genome CRISPR screen identifies the spindle accessory checkpoint as a locus of nab-paclitaxel resistance in pancreatic cancer cells.

ABSTRACT: A whole-genome CRISPR screen identifies the spindle accessory checkpoint as a locus of nab-paclitaxel resistance in pancreatic cancer cells.

PROVIDER: PRJNA1090475 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR28410434.fastq.gz	Fastqsanger.gz
	SRR28410435.fastq.gz	Fastqsanger.gz
	SRR28410436.fastq.gz	Fastqsanger.gz
	SRR28410437.fastq.gz	Fastqsanger.gz
	SRR28410438.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

A whole-genome CRISPR screen identifies the spindle accessory checkpoint as a locus of nab-paclitaxel resistance in pancreatic cancer cells.

Project description:Pancreatic adenocarcinoma is one of the most aggressive and lethal forms of cancer. Chemotherapy is the primary treatment for pancreatic cancer, but resistance to the drugs used remains a major challenge. A genome-wide CRISPR interference and knockout screen in the PANC-1 cell line with the drug nab-paclitaxel has identified a group of spindle assembly checkpoint (SAC) genes that enhance survival in nab-paclitaxel. Knockdown of these SAC genes (BUB1B, BUB3, and TTK) attenuates paclitaxel-induced cell death. Cells treated with the small molecule inhibitors BAY 1217389 or MPI 0479605, targeting the threonine tyrosine kinase (TTK), also enhance survival in paclitaxel. Overexpression of these SAC genes does not affect sensitivity to paclitaxel. These discoveries have helped to elucidate the mechanisms behind paclitaxel cytotoxicity. The outcomes of this investigation may pave the way for a deeper comprehension of the diverse responses of pancreatic cancer to therapies including paclitaxel. Additionally, they could facilitate the formulation of novel treatment approaches for pancreatic cancer.

2024-03-21 | GSE262149 | GEO

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

Effect of Gemcitabine and nab-paclitaxel in pancreatic cancer cachexia

Project description:The aim of the study is to test if Gemcitabine in combination with nab-paclitaxel can prevent muscle wasting and cardiac dysfunction in a mouse model of pancreatic cancer cachexia.

2025-04-04 | GSE234545 | GEO

A whole-genome CRISPR screen identifies the spindle accessory checkpoint as a locus of nab-paclitaxel resistance in pancreatic cancer cells.

| S-EPMC10896345 | biostudies-literature

RNA-seq analysis of SMARCA4-deficient NCI-H838 xenograft tumors treated with PRT3789, docetaxel, nab-paclitaxel, or combination regimens

Project description:The goal of this study was to examine transcriptional responses to the SMARCA2-selective degrader PRT3789, standard chemotherapies, and their combinations in SMARCA4-deficient NCI-H838 xenograft tumors. Six treatment groups were evaluated: (1) vehicle control, (2) PRT3789, (3) docetaxel, (4) nab-paclitaxel, (5) PRT3789 plus docetaxel, and (6) PRT3789 plus nab-paclitaxel. RNA-seq was performed on tumors collected 120 hours post–first dose to investigate treatment-specific gene expression signatures.

2025-09-12 | GSE307427 | 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

A whole-genome CRISPR screen identifies the spindle accessory checkpoint as a locus of nab-paclitaxel resistance in a pancreatic cancer cell line.

| S-EPMC11236977 | biostudies-literature

Nab-paclitaxel induces DNA damage and inhibits M2 polarization of macrophages to achieve radiosensitization of cholangiocarcinoma cells.

Project description:Through transcriptome sequencing, it was determined that AMPK is a key pathway involved in the radiosensitization effect of nab-paclitaxel, and its sensitization effect may be attributed to ZMAT3 and NF- κB signaling pathway is closely related.

2024-06-01 | GSE262746 | GEO

c-Myc drives nab-paclitaxel resistance in pancreatic cancer

Project description:c-Myc drives nab-paclitaxel resistance in pancreatic cancer

| PRJNA544707 | ENA

Effect of Gemcitabine and nab-paclitaxel in pancreatic cancer cachexia

Project description:Effect of Gemcitabine and nab-paclitaxel in pancreatic cancer cachexia

| PRJNA982000 | ENA