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DNA repair mechanisms and therapy resistance of BRCA2-deficient cancers

Total Cost €


EC-Contrib. €






 DREMATURE project word cloud

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

ovarian    inhibitors    start    employ    rely    mimics    hr    reduces    screens    despite    deficient    parpi    believe    occurs    synergizing    treatment    damage    animals    repair    organoid    visualize    engineered    candidate    mechanisms    crispr    disseminated    genes    dna    genetically    whereas    brca2    vitro    treatments    decision    clinical    human    lack    cells    physiologically    survive    escape    yielded    drug    strategies    am    interesting    tumors    death    sequencing    molecular    driving    ribose    spontaneous    imaging    biosensors    closely    polymerase    convinced    expertise    generation    efficacy    existence    cas9    lethality    anti    mouse    alternative    patients    sophisticated    homologous    oncology    synthetic    specificity    claspin    patient    breast    resistance    therapy    survival    strategy    cancers    modern    intact    cultures    cancer    model    function    innovative    vivo    poly    functional    normal    largely    dynamics    brca1    recombination    unknown    overcome    jammed    resistant    3d    smart    defect    mdc1    tumor    disease    candidates    basic    genetic    image    die    adp    combination   

Project "DREMATURE" data sheet

The following table provides information about the project.


Organization address
city: BERN
postcode: 3012

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 Switzerland [CH]
 Total cost 187˙419 €
 EC max contribution 187˙419 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-01-01   to  2019-12-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAET BERN CH (BERN) coordinator 187˙419.00


 Project objective

Despite the existence of various novel anti-cancer treatments, drug resistance remains a major cause of death in patients with disseminated cancer. To increase specificity and efficacy, modern treatment strategies in molecular oncology employ the “synthetic lethality” concept. An example are BRCA1/2-deficient breast and ovarian cancers that lack DNA repair by homologous recombination (HR). Due to this defect, tumor cells rely more on other DNA repair pathways. When such alternative pathways are jammed, e.g. by poly(ADP-ribose) polymerase inhibitors (PARPi), normal cells with intact HR can survive, whereas cancer cells die. However, even with this sophisticated treatment strategy, resistance to PARPi still occurs and greatly reduces patient survival. The mechanisms driving this resistance are still largely unknown. The main goal of this project is to advance the knowledge on therapy resistance by using a genetically engineered mouse model of BRCA2-deficient breast cancer, which closely mimics the human disease. Like in patients, cancer cells in these animals eventually escape from therapy. I will start by synergizing the next generation sequencing analysis of spontaneous resistant mouse tumors with functional genetic screens using the CRISPR/Cas9 technology. This combination has yielded interesting candidate genes whose loss of function may cause resistance. Two promising candidates, MDC1 and Claspin, will be further investigated using innovative and physiologically relevant 3D tumor organoid cultures. Moreover, I will apply my expertise in modern imaging technology to develop novel approaches to visualize DNA repair dynamics in resistant tumors in vitro and in vivo. I am convinced that by understanding basic resistance mechanisms, smart biosensors can be built to image the DNA damage response and eventually improve clinical decision making. I believe this project will have an impact on the design of strategies to overcome therapy escape in human cancer patients.

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The information about "DREMATURE" are provided by the European Opendata Portal: CORDIS opendata.

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