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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.

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

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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