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BRCAstem SIGNED

Monitoring cancer stem cell dynamics and therapeutic response in BRCA2-deficient breast tumour cells

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 BRCAstem project word cloud

Explore the words cloud of the BRCAstem project. It provides you a very rough idea of what is the project "BRCAstem" about.

upregulation    survival    metastatic    days    acquire    intrinsic    vulnerabilities    breast    cancer    st    xenografts    pancreatic    population    initiating    monitor    tumorigenesis    inactivation    signature    28    metastasis    carriers    experimental    mechanisms    heterozygous    ovarian    polymerase    susceptibility    markers    rna    temporal    ionizing    single    transcriptomics    genomic    accumulated    understand    sub    driving    subpopulations    sequencing    radiation    enrichment    brca2    lacking    mutated    spatio    tumours    brca    cell    laboratory    scrna    germ    plasticity    spatial    heterogeneity    adp    capacity    instability    patient    suggesting    cells    combined    propagation    line    mechanism    relationship    seq    relevance    host    cancers    dynamics    poly    genes    inhibitors    resistance    brca1    abrogation    ribose    therapy    underlying    impacts    mutations    csc    deficient    prostate    personalized    stem    lines    cscs    models    molecular    parp    pdxs    ir    predispose    intend    therapies    resolution    tumour   

Project "BRCAstem" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD 

Organization address
address: WELLINGTON SQUARE UNIVERSITY OFFICES
city: OXFORD
postcode: OX1 2JD
website: www.ox.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 224˙933 €
 EC max contribution 224˙933 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2019
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2020
 Duration (year-month-day) from 2020-07-01   to  2022-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD UK (OXFORD) coordinator 224˙933.00

Map

 Project objective

Heterozygous germ line mutations in the breast cancer susceptibility genes (BRCA) 1 or 2 predispose carriers to breast, ovarian, pancreatic and prostate cancers. Significant evidence has accumulated in recent years on vulnerabilities specific to BRCA1/2-deficient tumours, leading to the development of personalized therapies, such as poly-ADP ribose polymerase (PARP) inhibitors. However, tumours develop resistance to these therapies, with tumour heterogeneity and enrichment in cancer stem cell (CSC) sub-population as an underlying resistance mechanism. How the genomic instability intrinsic to BRCA1/2 inactivation impacts on CSC survival and propagation during tumorigenesis and their relevance to the response to therapy has not yet been established. Previous results obtained in the host laboratory show that BRCA2 loss is associated, in the long term (28 days after BRCA2 abrogation), with upregulation of genes involved in metastasis and CSC markers, suggesting BRCA2-deficient cells can acquire metastatic and tumour-initiating capacity. In the current project proposal, we intend to study at single-cell resolution the relationship between CSCs and the response to PARP inhibitors and ionizing radiation (IR) in cancer cell lines and patient-derived xenografts (PDXs) lacking BRCA2 . We will develop a combined single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) experimental approach to characterize BRCA2-deficient CSC subpopulations and to monitor the spatio-temporal dynamics of the CSC signature. This will enable us not only to understand the molecular mechanisms driving cell plasticity in models of BRCA2 inactivation, but also to evaluate the CSC impact on the response of BRCA-mutated tumours to current targeting therapies.

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The information about "BRCASTEM" are provided by the European Opendata Portal: CORDIS opendata.

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