Objective
Chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is addicted of interactions with the microenvironment. The B-cell receptor (BCR) is one of the most important surface molecules that CLL cells use to gain oncogenic signals from the microenvironment. The critical role of BCR signaling for the pathogenesis of CLL is supported by the therapeutic success of ibrutinib, a targeted agent that disrupts the BCR pathway. Beside microenvironment-promoted oncogenic signals, the biology of CLL is also driven by molecular lesions and clonal evolution, that mark CLL progression and treatment resistance. The interconnection between microenvironment-promoted oncogenic signals and clonal evolution has been postulated in CLL but never proven because of the lack of suitable ex vivo models. Ibrutinib allows the unprecedented opportunity of assessing the contribution of cell signaling to cancer clonal evolution directly in vivo in patients. The project working hypothesis is that mutation- and selection-driven clonal evolution is promoted by microenvironment-induced signals, including those propagated from the BCR. According to this hypothesis: i) BCR signaling inhibition due to ibrutinib should stop clonal evolution; while ii) acquisition of by-pass mechanisms that keep ongoing signaling should promote mutation and selection despite BCR inhibition, thus favoring CLL clonal evolution and ibrutinib resistance. In this scenario, the combination of ibrutinib with drugs that overcome by-pass mechanisms could prevent clonal evolution, thus improving treatment efficacy and patient outcome. In order to address our working hypothesis, we will take advantage of clinical trial and co-clinical trial samples to monitor signaling and clonal evolution under ibrutinib and ibrutinib-based combination treatments.
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 cell biology cell signaling
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology leukemia
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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.1.1. - EXCELLENT SCIENCE - 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.
ERC-COG - Consolidator Grant
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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-2017-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.
6500 Bellinzona
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.