Objective
Lung adenocarcinoma is the most frequent subtype of lung cancer and patients harbour activating mutations in the KRAS gene in approximately 25% of the cases. Unfortunately, regardless of the outcome of recent studies identifying specific KRASG12C inhibitors, so far, oncogenic KRAS is not a druggable target yet. The best-characterized KRAS effector pathway, the ERK cascade consists of RAF, MEK and ERK proteins that can be inhibited with small molecules targeting their kinase activities. As the development of RAF and MEK kinases inhibitors progressed, feedback loop reactivating the ERK cascade have emerged, inducing resistance to treatment. Thus, new innovative strategies are needed to achieve a more long-term inhibition of this signalling pathway, while reducing detrimental side effects due to MAPK inhibition in normal cells. It has been described more than 20 years ago that RAF directly interacts with RAS through its Ras Binding Domain (RBD), and many research groups have been trying to disrupt this interaction developing allosteric inhibitors as a cancer therapy. At the moment, those molecules need to be improved in order to achieve a strong inhibition of this pathway. Surprisingly, no mouse model actually demonstrates the requirement of RAS/RAF interaction during KRAS-induced lung tumourigenesis. Here, we propose to investigate this crucial question using a new mouse model allowing us to conditionally disrupt RAS/RAF interaction in vivo. Using the leading mouse model to study lung cancer (LSL-KrasG12D/+; p53-/- mice), we will take advantage of both Cre/LoxP and FLIPo/Frt technologies to investigate the role of RAS/RAF interaction during lung tumours maintenance, as well as its function in tumour/host crosstalk and normal physiology. All together, these investigations will provide important insights into the clinical relevance of developing RAS interaction inhibitors for the treatment of RAS-driven tumours.
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 basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences clinical medicine oncology prostate cancer
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine oncology lung cancer
- medical and health sciences basic medicine physiology
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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.
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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-EF-ST - Standard EF
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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-2016
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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.
NW1 1AT London
United Kingdom
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.