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

Total Cost €


EC-Contrib. €






 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.

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

Project "AR-DDR" data sheet

The following table provides information about the project.


Organization address
address: CALLE NAZARET 115-117
postcode: 8035

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


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 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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