Objective
Tumors are ecosystems in which cancer cells interact with diverse cell populations. In each such ecosystem, environmental conditions, cellular compositions and paracrine signaling create a distinct tumor habitat. How much the composition of the habitat is dictated by the organ versus specific mutations in the cancer cells is unknown. If different organs and mutations have common microenvironmental design principles, one could devise more general therapy. Otherwise, therapy must be mutation and organ specific.
To approach this, we will focus on major cancer mutations in BRCA1/2 and on the four organs where BRCA mutations drive cancer: breast, ovary, pancreas and prostate. We will dissect microenvironments of BRCA-driven cancers in these organs using a wide arsenal of imaging, sequencing, and molecular tools, building on our recent discovery of distinct cancer-associated fibroblast (CAF) compositions in BRCA-mutated breast cancer. To untangle complexity, we will establish a new approach to calibrate mathematical models on ex-vivo cocultures, and use it to identify testable targets.
First, we will define the configuration of CAF subsets in the four organs, comparing BRCA-mutated to BRCA-WT human tumors (Aim 1). To unravel signaling loops common and different between organs, we will explore fibroblast dynamics in normal tissues and their diseased counterparts by ex-vivo cocultures and mathematical modeling (Aim 2). We will leverage this knowledge to design CAF inhibitors and combine them with BRCA-specific therapies in cocultures and preclinical models, to address a major unmet clinical need to exploit CAF vulnerabilities for cancer therapy (Aim 3).
This program provides a conceptual paradigm for understanding the principles of tumor microenvironment habitats, using BRCA as a testcase and four organs of clinical interest as model systems. This paradigm will be directly applicable to the major mutation classes and organ environments of cancer.
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.
- medical and health sciences clinical medicine oncology prostate cancer
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences ecology ecosystems
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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)
- Tumor microenvironment
- cancer-associated fibroblasts
- tumor heterogeneity
- extracellular matrix
- BRCA1
- 2
- multiplexed immunofluorescent imaging
- image analysis
- breast cancer
- ovarian cancer
- pancreatic cancer
- prostate cancer
- single cell RNA sequencing
- transcriptional profiling
- cancer therapy
- PARP-inhibitors
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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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
HORIZON-ERC - HORIZON ERC Grants
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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) ERC-2021-COG
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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.
7610001 Rehovot
Israel
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.