Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA sequencing of luminal breast cancer patient-derived xenografts (PDX) library to capture tumor heterogeneity and explore the mechanisms of resistance to CDK4/6 inhibitors

ABSTRACT: Combining CDK4/6 inhibitors (CDK4/6i) with endocrine therapy has proven clinically effective and represents now the first-line treatment for advanced Luminal Breast Cancer (LBC) patients. However, resistance to CDK4/6i almost invariably arises in these patients, emphasising the critical need to comprehend these mechanisms and develop new strategies to overcome resistance. We report on the generation and characterisation of a LBC PDX displaying acquired resistance to CDK4/6i palbociclib. Treating a sensitive luminal BC PDX with the CDK4/6i palbociclib revealed that, despite initial tumour shrinkage, some tumours might eventually regrow under drug treatment. RNA sequencing, followed by gene set enrichment analyses, unveiled that this PDX have become refractory to CDK4/6i, both at biological and molecular level.

INSTRUMENT(S): NextSeq 550

ORGANISM(S): Homo sapiens

SUBMITTER: Barbara Belletti

PROVIDER: E-MTAB-14085 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Single cell RNA Seq to study the effects of Palbociclib in the mouse LSK cell compartment

Project description:To understand how Palbociclib (a CDK4/6 inhibitor) treatment changes the transcriptome of hematopoietic stem and progenitor cells, wildtype cells were isolated from mice and treated for 24h with either PBS (control) or Palbociclib. After 24h of culture, the cell suspensions were collected and sorted for lineage-negative, Sca1-positive, cKit-positive (LSK) cells which were subjected to library prep for single cell RNA sequencing.

2024-05-22 | E-MTAB-13268 | biostudies-arrayexpress

Characterizing the Chemoresistant Ovarian Cancer Population using the Heterogeneous PDX

Project description:The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy across a population, but also study crucial aspects of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor’s heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. The pathways most significantly altered included Protein Kinase A signaling, GNRH signaling, and sphingosine-1-phosphate signaling. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer 6 pairs of Patient-Derived Xenografts (PDX) were ananlyzed using RNA-seq for a total of 12 samples. Each pair consists of a treated and untreated PDX of ovarian cancer. Treated Ovarian cancer PDXs were treated with 4 weeks of a combination of carboplatin and taxol. RNA was isolated and converted to cDNA. RNA-seq was conductred on the Illumina HiSeq 2000 with 50 bp paired end sequencing

2015-06-17 | E-GEOD-58586 | biostudies-arrayexpress

Spatial transcriptomic analysis of Sonic Hedgehog Medulloblastoma identified that loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition

Project description:We used spatially resolved transcriptomics to define the cellular diversity within a sonic hedgehog (SHH) patient-derived model of Medulloblastoma (MB) and identify how cells specific to a transcriptional state or spatial location are pivotal in responses to treatment with the CDK4/6 inhibitor, Palbociclib. Our analysis reveals that SHH tumour in the mouse brain contains multiple malignant transcriptional states, recapitulating the extent of intratumoural cellular diversity identified in primary human SHH MB. Our study offers new insight into the previously described features of CDK4/6 inhibition in MB, with Palbociclib treatment inducing neuronal differentiation across all remaining cell types comprising the bulk of the SHH patient-derived orthotropic xenograft model. This study is, to the best of our knowledge, the first spatially resolved gene expression atlas of SHH PDOX MB and acts as proof-of-principle for the use of ST-seq in identifying spatially-organised tumour heterogeneity of MB.

2022-06-16 | E-MTAB-11720 | biostudies-arrayexpress

Identification of tumor antigens in the HLA peptidome of patient-derived xenograft tumors in mouse

Project description:Personalized cancer immunotherapy targeting patient-specific cancer/testis (CTA) antigens and neoantigens may benefit from large-scale tumor HLA peptidome (immunopeptidome) analysis, which aims to accurately identify antigens presented by tumor cells. While significant efforts have been invested in analyzing the HLA peptidomes of fresh tumors, it is often impossible to obtain sufficient volumes of tumor tissues for comprehensive HLA peptidome characterization. This work attempted to overcome some of these obstacles by using patient-derived xenograft tumors (PDX) in mice as the tissue sources for HLA peptidome analysis. PDX tumor provide a proxy for expansion of the patient tumor by re-grafting them through several passages to immune compromised mice. The HLA peptidomes of human biopsies were compared to those derived from PDX tumors. Larger HLA peptidomes were obtained from the significantly larger PDX tumors as compared to the patient biopsies. The HLA peptidomes of different PDX tumors derived from the same source tumor biopsy were very reproducible, even following subsequent passages to new naïve mice. A large number of CTA-derived HLA peptides were discovered, as well as several neoantigens. Taken together, use of PDX tumors for HLA peptidome analysis serves as a highly expandable and stable source of reproducible and authentic peptidomes, opening up new opportunities for defining large HLA peptidomes when only small tumor biopsies are available. This approach provides a large source for tumor antigens identification potentially useful for personalized immunotherapy.

2020-05-27 | PXD016060 | Pride

Label-free proteomics quantification of pancreatic ductal adenocarcinoma patient-derived xenografts with treatment combining Gemcitabine and nab-Paclitaxel

Project description:Tumor-stroma interactions are critical in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutics. Patient-derived xenograft (PDX) models faithfully recapitulate tumor-stroma interactions in PDAC, but conventional antibody-based immunoassay is largely inadequate to resolve or quantify tumor and stromal proteins. A species-deconvolved proteomics approach embedded in the ultra-high-resolution (UHR)-IonStar workflow can unambiguously quantify the proteins from tumor (human-derived) and stroma (mouse-derived) in PDX samples, enabling unbiased investigation of their proteomes with excellent quantitative reproducibility. With this strategy, 3 PDAC PDXs were analyzed. They were showed differential responses to treatment with Gemcitabine combined with nab-Paclitaxel (GEM+PTX), which is a first-line treatment regimen for PDAC. For each PDAC PDX, samples were collected after 24 hour and 192 hour with/without treatment, and each condition contained four biological replicates.

2023-07-05 | PXD042267 | Pride

Targeting kinome reprogramming in ESR1 fusion-driven metastatic breast cancer

Project description:Transcriptionally active ESR1 fusions promote endocrine therapy (ET)-resistant growth and metastasis of estrogen receptor-alpha positive (ERα+) breast cancer. Currently, there are no targeted treatment options for tumors harboring active fusions because the ESR1 ligand binding domain (LBD) has been replaced with non-drug binding sequences from the 3’ partner gene. A mass spectrometry (MS)-based Kinase Inhibitor Pulldown Assay (KIPA) demonstrated an increase of multiple receptor tyrosine kinases including RET in T47D cells expressing active ESR1 fusions. Integrated proteogenomics defined tumor subsets that could be responsive to RET and CDK4/6 directed therapy from 22 biologically heterogeneous ERα+ patient-derived xenograft (PDX) tumors. Inhibition of RET by repurposing an FDA-approved drug significantly suppressed ESR1 fusion-driven growth of cell, PDX-derived organoid (PDXO) and PDX models. CDK4/6 inhibitor treatment showed similar tumor reductions to RET inhibition. Here, we reveal therapeutic kinase vulnerabilities in ESR1 fusion-driven tumors, which will lay the framework for future clinical trials.

2023-10-24 | PXD033339 | Pride

Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies unique proteotypes associated with patient outcomes

Project description:We generated PDX models of aggressive NSCLC, which represent the DNA methylation features modelling of primary NSCLC

2021-11-24 | E-MTAB-10156 | biostudies-arrayexpress

Increased cholesterol biosynthesis identified as a key feature and a therapeutic target of cancer stem cells as revealed by proteomic comparison of clinical breast cancer tissue and corresponding patient-derived xenografts and mammospheres

Project description:Cancer stem cells (CSCs) comprise a small subpopulation of undifferentiated cancer cells with the ability to self-renew and give rise to the heterogeneous cancer cell lineages that form tumorous masses. Thus, tumor eradication may be greatly improved by specifically targeting CSCs, as they exhibit resistance to conventional therapy. To gain insight into the unique biology of CSCs, we developed patient-derived xenograft (PDX) tumors from ER-negative breast cancer patient tissue from which we isolated mammospheres, a method known to enrich for cells with CSC-properties. An unbiased, comparative global proteomic analysis using label-free mass spectrometry was performed on the patient tumor tissues and corresponding PDX tumors and mammospheres. Good concordance between the proteome profiles of patient tumor tissue and corresponding PDX tumors was observed. However, lower abundance of immune- and extracellular matrix-related proteins and higher abundance of proteins associated with cell-to-cell adhesion including desmosome proteins and β-catenin were observed in PDX versus patient tumors. Interestingly, analysis of proteins elevated in mammospheres vs. PDX tumors identified an enrichment of proteins associated with de novo cholesterol synthesis. The clinical relevance of increased cholesterol biosynthesis protein expression was verified in a large gene expression data set of clinical breast cancers showing correlation with shorter relapse-free survival. RNA interference and chemical inhibition of the cholesterol biosynthesis pathway reduced mammosphere formation and growth of CSCs derived from PDX tumors and cancer cell lines. Our findings identify the cholesterol biosynthesis pathway as central for CSC growth and a potential therapeutic target for CSC as well as providing an additional mechanistic explanation for the observed benefit of statins in breast cancer treatment.

2019-07-02 | PXD011222 | Pride

leChRO-seq for 2 pancreatic cancer patient-derived xenografts treated with Vehicle or Gemcitabine/Paclitaxel in mouse

Project description:Evaluation of nascent RNA in PDX

2023-03-21 | E-MTAB-11740 | biostudies-arrayexpress

RNA-Seq of rheumatoid arthritis synovial fibroblasts treated with CDK4/6 inhibitor and TNF+IL-1b stimulation

Project description:We prepared five RASF samples from each donor under four conditions: in the presence or absence of CDK4/6 inhibitor, palbociclib, and with or without cytokine stimulations. In total, 20 samples were analyzed. RASFs were treated with CDK4/6 inhibitor for 24 hours in advance to the stimulation. RNA was collected after 24 hours of the stimulation(TNF+IL-1b, 0.2ng/ml each)

2023-01-26 | E-MTAB-10795 | biostudies-arrayexpress

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