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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.

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

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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