Objective
Genomic instability characterizes tumors, which have no clear ‘oncogenic-driver’ mutation, including triple-negative breast cancers (TNBCs). These patients do not benefit from molecularly targeted treatment and urgently need better treatment options. Increasing evidence points to replication stress as the driver of genomic instability. Since replication stress compromises cell viability, cells have evolved mechanisms to mitigate this threat.
Recently, I discovered a novel cellular mechanism—mitotic Replication Stress Recovery (RSR)—that acts as an ‘emergency brake’ during mitosis, allowing recovery from high levels of replication stress. This machinery is critical for tumor cell survival, and therefore constitutes a promising target for anti-cancer drug development. However, it is unclear how this mitotic RSR is organized molecularly and how it can be targeted therapeutically.
In this project, I aim to molecularly define and therapeutically target the Mitotic Replication Stress Recovery (RSR) machinery in triple-negative breast cancer cells.
To this end, I will implement a series of complementary innovative strategies. First, I will use mass-spec-based proteomics to molecularly characterize components and wiring of the mitotic RSR machinery. Second, to identify the genetic profiles of cancer subgroups that are sensitive to inactivation of the mitotic RSR, functional genetic screens will be combined with visualization and quantification of replication stress in genomically-defined human cancer samples. Finally, my findings will be translated to the pre-clinical situation by exploring the feasibility of therapeutic inactivation of the RSR machinery in vitro and in vivo in a panel of triple-negative breast cancer models.
In summary, TENSION will provide advanced insight into the composition and wiring of the mitotic RSR machinery and will reveal the potency of targeting this pathway therapeutically for TNBCs and other hard-to-treat, genomically instable cancers.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
-
H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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.
ERC-COG - Consolidator Grant
See all projects funded under this funding scheme
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) ERC-2015-CoG
See all projects funded under this callHost institution
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.
9713 GZ Groningen
Netherlands
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.