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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.

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

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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