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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors biosensors
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- medical and health sciences clinical medicine oncology breast cancer
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2016
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
3012 BERN
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.