Objective
Tumor metastases, relapse, and resistance to therapy are the main causes of death in cancer patients. Cancer stem cells (CSCs) drive cancer growth, are likely responsible for cancer reoccurrence, and provide the potential to colonize a metastatic site. A cell plasticity process called epithelial-mesenchymal transition (EMT) generates CSCs from epithelial cancer cells and simultaneously equips these cells with motility and invasiveness, features prerequisite for metastasis. Consequently, therapeutic strategies that target EMT and CSC signaling networks are highly attractive. However, the properties of these signaling networks and their dependency on the tumor microenvironment and cancer genotypes are poorly understood. Here we propose to generate quantitative, time-resolved biomarker signatures and network models of EMT stages and CSCs on the single-cell level and to define their dependency on breast cancer tumor microenvironments and genotypes. Using mass cytometry, a technology able to quantify up to 100 proteins and phosphorylation sites simultaneously in a single-cell, the signaling network structure of EMT and CSC state will be gauged by modulation of cancer-related and signaling genes. These data will be used to infer mathematical signaling network descriptions of EMT and the CSC states, and to determine their master regulators and regulatory sub-networks. By extending mass cytometry to spatially resolved measurements, the EMT/CSC network states and their microenvironment will be analyzed in three dimensions in patient samples, and data will be correlated with associated genomic and clinical information. Based on these in vivo data, follow-up experiments in mouse models will be performed to validate the identified network states and cell-to-cell interaction as therapeutic targets. Finally, the in vivo dataset and its correlation with genomic and clinical information will be used to identify biomarkers for personalized medicine approaches.
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 biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology breast cancer
- medical and health sciences health sciences personalized medicine
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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.
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.
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.
ERC-2013-StG
See other projects for this call
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.
Host institution
8006 ZURICH
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.