Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression analyses of palbociclib treated ER+ breast cancer cell lines as assessed by RNA-seq

ABSTRACT: Gene expression analyses of palbociclib treated ER+ breast cancer cell lines as assessed by RNA-seq

PROVIDER: PRJNA623621 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11505248_1.fastq.gz	Fastqsanger.gz
	SRR11505248_2.fastq.gz	Fastqsanger.gz
	SRR11505249_1.fastq.gz	Fastqsanger.gz
	SRR11505249_2.fastq.gz	Fastqsanger.gz
	SRR11505250_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 30

Similar Datasets

Gene expression analyses of palbociclib treated ER+ breast cancer cell lines as assessed by RNA-seq

Project description:The goal of this study is to measure gene expression changes resulting over time of palbociclib treatment of T47D, MCF7, and CAMA1 ER+ breast cancer cell lines.

2020-12-28 | GSE148265 | GEO

Gene expression analysis of ER+ and ER- breast cancer cell lines with acquired resistance to palbociclib

Project description:While targeted therapies directed against cancer cells have proven effective, their clinical benefit is often limited by acquired resistance. This clinical challenge underscores the importance of uncovering the molecular mechanisms behind resistance in order to develop novel targets and drug combinations that can stop the growth of cancer cells. Two pivotal pathways controlling tumor growth are glucose metabolism and cell cycle. PFKFB3 and CDK4/6 are key regulators of glucose metabolism and cell cycle respectively for which inhibitors have been developed. PFK158 is an inhibitor against PFKFB3 that is currently undergoing phase I clinical trials and has shown to be effective at blocking glucose metabolism in solid tumors. Palbociclib, a novel CDK4/6 inhibitor was recently approved as a first-line approach for the treatment of estrogen receptor (ER) positive breast cancer because of the very promising clinical responses in ER+ breast cancer patients. Unfortunately, the effects of these therapies are short-lasting since cancer cells ultimately develop resistance allowing them to escape treatment. To identify the molecular mechanisms driving resistance to PFK158 or palbociclib, we have generated ER+ MCF7 and ER- MDA-MB231 cells resistant to either PFK158 or palbociclib by continuous exposure to increasing doses of drugs for a period of three months. Our hypothesis is that resistance is driven by activating mutations and/or pathways acquired during the course of treatment. This study is designed to identify specific mutations and/or changes in gene expression responsible for the resistance to PFK158 or palbociclib in ER+ and ER- in vitro. The results of this study will lead to the development of new therapeutic strategies to overcome resistance to PFKFB3 and CDK4/6 inhibitors.

2019-06-20 | GSE130437 | GEO

Gene expression analysis of ER+ and ER- breast cancer cell lines with acquired resistance to palbociclib

Project description:Gene expression analysis of ER+ and ER- breast cancer cell lines with acquired resistance to palbociclib

| PRJNA540259 | ENA

Palbociclib resistance analyses on breast cancer bone metastasis PDX

Project description:Identify mecanisms of metastatic breast cancer resistance to palbociclib by RNAseq analyses.

| EGAS00001006428 | EGA

Oxidative phosphorylation is a metabolic vulnerability of endocrine therapy and palbociclib resistant metastatic breast cancers

Project description:Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic and metabolomics analyses of patients' tumours, metastasis-derived patient-derived xenografts (PDX) and isogenic cell lines we demonstrate that a fraction of metastatic ER + BC is highly reliant on oxidative phosphorylation (OXPHOS). Treatment by the OXPHOS inhibitor IACS-010759 strongly inhibits tumour growth in multiple endocrine and palbociclib resistant PDX. Mutations in the PIK3CA/AKT1 genes are significantly associated with response to IACS-010759. At the metabolic level, in vivo response to IACS-010759 is associated with decreased levels of metabolites of the glutathione, glycogen and pentose phosphate pathways in treated tumours. In vitro, endocrine and palbociclib resistant cells show increased OXPHOS dependency and increased ROS levels upon IACS-010759 treatment. Finally, in ER + BC patients, high expression of OXPHOS associated genes predict poor prognosis. In conclusion, these results identify OXPHOS as a promising target for treatment resistant ER + BC patients.

2023-06-27 | MTBLS3342 | MetaboLights

Short term (16 hour) treatment of ER+ breast cancer cell lines with low doses of CDK4/6 inhibition

Project description:Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression free survival for metastatic, estrogen receptor positive (ER+) breast cancers, but their role in the non-metastatic setting remains unclear. We sought to understand the effects of CDK4/6 inhibition (CDK4/6i) and radiation (RT) in multiple preclinical breast cancer models. Transcriptomic and proteomic analyses were used to identify significantly altered pathways after CDK4/6i. Clonogenic assays were used to quantify the RT enhancement ratio (rER). DNA damage was quantified using γH2AX staining and the neutral comet assay. DNA repair was assessed using RAD51 foci formation and non-homologous end joining (NHEJ) reporter assays. Orthotopic xenografts were used to assess the efficacy of combination therapy. Palbociclib significantly radiosensitized multiple ER+ cell lines at low nanomolar, sub IC50 concentrations (rER: 1.21 – 1.52) and led to a decrease in the surviving fraction of cells at 2 Gy (p < 0.001). Similar results were observed in ribociclib- (rER: 1.08 - 1.68) and abemaciclib-treated (rER: 1.19 - 2.05) cells. Combination treatment decreased RAD51 foci formation (p < 0.001), leading to a suppression of HR activity, but did not affect NHEJ efficiency (p > 0.05). Immortalized breast epithelial cells and cells with acquired resistance to CDK4/6i did not demonstrate radiosensitization (rER: 0.94 – 1.11) or changes in RAD51 foci. In xenograft models, concurrent palbociclib and RT led to a significant decrease in tumor growth. These studies provide preclinical rationale to test CDK4/6i + RT in women with locally-advanced ER+ breast cancer at high risk for locoregional recurrence.

2020-09-24 | GSE155570 | GEO

TUMOUR KINOME RE-WIRING GOVERNS RESISTANCE TO PALBOCICLIB IN OESTROGEN RECEPTOR POSITIVE BREAST CANCERS, HIGHLIGHTING NEW THERAPEUTIC MODALITIES

Project description:Estrogen receptor positive (ER+) breast cancers are the most common type of breast cancer. Despite the great efficacy of endocrine therapies, resistance remains a problem. Therefore, there is an immediate need for new, effective therapies in ER+ BC. In this study, we have explored the role of a potent CDK4/6 inhibitor called palbociclib. In order to identify differential phosphoproteomic events that underpin the mode of action and recurrence for this treatment, we generated a panel of palbociclib-sensitive and resistant cell lines and did quantitative, shotgun phosphoproteomics using titanium IMAC. Palbociclib sensitive cell lines (wt-MCF7 or MCF7-LTED) were cultured in phenol red-free RPMI supplemented with 10% FBS and 1nM estradiol or 10% dextran-coated charcoal (DCC) respectively. Thereafter, palbociclib resistant cell lines were generated using 1μΜ palbociclib concentration. Samples were harvested at baseline and at the point of resistance.

2020-04-29 | PXD005514 | Pride

Combined inhibition of STAT3 and DNA repair in palbociclib-resistant ER-positive breast cancer

Project description:The results from our study have identified two clinically relevant, divergent and druggable pathways (DNA repair and STAT3) that can be targeted in combination to effectively combat drug resistance. We also found that the same pathways that were deregulated in palbociclib-resistant cells were also altered in tumor samples obtained from patients who progressed while on palbociclib and endocrine therapy

2019-08-31 | GSE128056 | GEO

RNA-seq of human breast cancer cell lines MCF7 and T74D naive and resistant to palbociclib treated with capivasertib, fulvestrant and combination

Project description:T47D and MCF7 cell lines were treated with long-term (continuous) palbociclib to induce 4 resistant cell-lines (T47D RB-, T47D CDK6H, MCF7 RB- and MCF7 PacqR). Each cell line (both parental and resistant) were then treated with DMSO (control), capivasertib monotherapy, fulvestrant monotherapy and capivasertib/fulvestrant combination. RNA data is available after each treatment and resistant cell lines additionally have RNA data available after continuous palbociclib treatment.

2023-08-14 | E-MTAB-13262 | biostudies-arrayexpress

Efficacy of abemaciclib in palbociclib-resistant hormone receptor positive breast cancer cell lines: MCF-7 and T47D

Project description:Resistance to CDK4/6 inhibitors plus endocrine therapy, standard of care for HR+/HER2-neg metastatic breast cancer (MBC) patients, remains as a clinical problem with limited therapeutic options after disease progression. Treatment with abemaciclib after progression on a prior CDK4/6i has received increasing interest. However, molecular predictors of cross-resistance and unique mechanism of resistance to each CDK4/6i are unknown. In this study, multiomics analyses revealed ≥30 differentially altered pathways between palbociclib and abemaciclib resistant models. Mechanistic, preclinical and retrospective clinical evidence showed that HR+/HER2-neg MBC tumors refractory to palbociclib still may be responsive to abemaciclib. Based on the unique mechanisms of resistance to each CDK4/6i, we propose that patients who would benefit from abemaciclib treatment post progression on palbociclib could be selected based on the Hallmark gene set enrichment of G2/M pathway, while those who most probably would be refractory could be identified base on the gene set enrichment of OXPHOS pathway.

2023-07-10 | GSE222367 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data