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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.

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

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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