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AR-DDR SIGNED

Co-targeting androgen receptor signalling and DNA damage repair for precision therapy in advanced prostate cancer

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 AR-DDR project word cloud

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

designed    training    mcrpc    academic    prior    therapies    atr    inform    castration    sensitive    data    care    hypothesize    repair    androgen    defects    genomic    scientist    chip    modulated    position    events    stage    host    dna    cas9    parallel    damage    vulnerabilities    resistant    sensitivity    genes    patients    heterogeneity    co    cross    genomics    options    atm    assays    correlated    plan    regulated    inhibition    contributed    transcriptional    crisrp    receptor    precise    ar    world    biopsies    opportunity    synthetic    2nd    mcprc    receiving    career    cancer    modulate    prostate    recombination    inhibitors    stratification    refine    optimal    combination    independence    fellowship    patient    seq    ddr    optimize    pursued    metastatic    primarily    physician    regulation    characterise    harbour    tests    inter    25    homologous    models    parp    functional    renders    acquired    plans    tp53    disease    pk    clinical    treatment    personalised    lethal    function    immunofluorescence    therapeutic    pursue    western    clinic   

Project "AR-DDR" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON 

Organization address
address: CALLE NAZARET 115-117
city: BARCELONA
postcode: 8035
website: http://www.vhio.net

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 Spain [ES]
 Total cost 172˙932 €
 EC max contribution 172˙932 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-05-01   to  2021-07-21

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON ES (BARCELONA) coordinator 172˙932.00

Map

 Project objective

Prostate cancer is the 2nd most common cancer in the western world. The advanced stage, metastatic castration-resistant prostate cancer (mCRPC), is a lethal disease. Understanding inter-patient genomic heterogeneity renders the opportunity to advance towards personalised patient care. Prostate cancer is a disease primarily driven by the androgen receptor (AR) pathway; however, the applicant prior work contributed to identifying 1) that up to 25% of mCRPC harbour defects in DNA damage repair (DDR) genes, and 2) that some of these mCPRC patients with DDR defects are sensitive to targeted treatment with PARP inhibitors. In the proposed research plan, we aim to exploit the cross-regulation between AR and DDR pathways to optimize precise therapeutic options for mCRPC patients. To achieve the objectives, the applicant will use models generated at the host through CRISRP/Cas9 to pursue functional studies and characterise how defects in ATM impact DDR function and sensitivity to inhibitors of PARP, ATR and DNA-PK. We hypothesize such sensitivity would be modulated by co-targeting of the AR pathway and by second events such as TP53 loss-of-function. ChIP-Seq assays will be pursued to identify genes co-regulated by the androgen receptor and PARP-1, to identify potential synthetic vulnerabilities. Then, mCRPC patient’s biopsies acquired in clinical practice from patients receiving AR-targeting therapies will be used to study how AR inhibition modulate transcriptional regulation of DDR pathways, to inform the optimal design of combination therapies. These data would be correlated with genomics and immunofluorescence tests of homologous recombination function, in order to refine patient stratification in the clinic. The proposed research will be conducted in parallel to a personalised training and career development plans, designed for the applicant to achieve a position of academic independence as physician-scientist before the end of the fellowship at the host institute.

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The information about "AR-DDR" are provided by the European Opendata Portal: CORDIS opendata.

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