Project description
Molecular insight into drug resistance mechanisms in breast cancer
Breast cancer ranks as one of the most prevalent forms of cancer in women today. Despite advances in targeted therapies, nearly 25 % of patients do not respond to treatment, or they develop drug resistance. The scope of the EU-funded NOSCAR project is to investigate the mechanisms of resistance to therapy. Scientists will focus on the oncogenic Ras/Erk and PI3K/Akt/mTOR signalling pathways known for their role in cell survival, proliferation, motility and metabolism. They will assess how these pathways are rewired in the presence of clinically relevant breast cancer mutations or following drug treatment. The project's results have the potential to identify novel targets for treating breast cancer in the future.
Objective
Despite significant progress in drug therapies for breast cancer, about one fourth of patients still do not survive the disease. Modern, targeted therapies have been proposed to cure the more advanced and aggressive cases of breast cancer. However, non-genetic and genetic mechanisms of drug resistance currently limit the promise of targeted therapy.
NOSCAR aims to define the oncogenic Ras/Erk and PI3K/Akt signalling states relevant to breast cancer oncogenic mutations, and delineate the mechanisms which enable development of cancer resistance to targeted therapies.
NOSCAR’s objectives are:
Using a quantitative cell biology framework that combines a multiplexed biosensor system that reports on Erk/Akt dynamics at single cell level, computer vision, and statistical modelling, I will:
(1) produce an atlas of single-cell Erk/Akt dynamic signalling patterns that are associated with a compendium of clinically-relevant breast cancer mutations;
(2) measure the signalling states in cells perturbed with clinically-relevant drugs that target different components of the Ras/Erk and PI3K/Akt pathways to evaluate how the oncogenic signalling network is rewired by drug treatment;
(3) measure signalling dynamics in 3D spheroid cultures and patient-derived organoids to explore how a self-organizing cellular ecosystem can spatially control signalling at the single cell level to locally control fate decisions, and how the latter process is compromised by an oncogenic mutation.
This will provide new insights about tumor heterogeneity and signaling network structures that confer robustness against drug perturbations. We expect to identify vulnerabilities that might be efficiently targeted by drug combinations, providing new avenues to treat breast cancer.
The planned research together with training and mentoring that I will receive thanks to the fellowship, will enable to successfully restart my career in research and will significantly benefit my further academic career prospects.
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.
- natural sciences computer and information sciences artificial intelligence computer vision
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- medical and health sciences clinical medicine oncology breast cancer
- natural sciences biological sciences genetics mutation
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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.
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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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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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-2019
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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.