Objective
Melanoma is among the most common and deadly human cancers. It kills more than 2000 people in the UK every year but an effective cure for metastatic disease does not exist yet.
The mutation of valine to glutamic acid at position 600 (V600E) of the BRAF kinase is found in over 60% of human melanomas, establishing it as a prominent oncogene in melanoma. Since this mutation is also commonly identified in benign and dysplastic nevi, the hypothesis is that additional mutations are required to induce melanomagenesis. Thus, a first challenge in the field is to identify those genetic events cooperating with oncogenic BRAFV600E in melanoma development, and exploit novel targets for combinatorial therapies.
Furthermore, the discovery of a central role for the BRAFV600E mutation in melanoma has led to the development of BRAFV600E-specific drug inhibitors. Initial clinical trials report extremely promising tumour regressions in the majority of patients. However, all patients eventually relapse after several months of treatment as a result of acquired resistance. I postulate that the therapeutic inhibition of BRAFV600E alone allows tumour cells to acquire additional yet unknown mutations that finally induce drug resistance and cancer’s regrowth. Therefore a second challenge is to understand the genetic determinants and molecular mechanisms responsible for the drug resistance to BRAFV600E inhibitors, which currently represent the most promising treatment option for melanoma. The aim of this project is to use novel mouse models of melanoma that develop in the setting of a Sleeping Beauty insertional mutagenesis to identify (i) genes cooperating with oncogenic BRAFV600E to promote melanoma and (ii) genes accountable for the development of drug resistance against BRAFV600E inhibitors.
Overall, the expected results in understanding the mechanisms of both melanomagenesis and resistance to BRAFV600E inhibitors will provide novel opportunities to develop effective melanoma therapeutics.
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 skin cancer melanoma
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- natural sciences biological sciences genetics mutation
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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.
FP7-PEOPLE-2010-IEF
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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.
Coordinator
CB10 1SA SAFFRON WALDEN
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.