Objective
The failure of anti-cancer therapies generally results from locally intractable invasive growth or from the presence of metastases refractory to treatment with curative intent. A novel therapeutic strategy is to develop new anti-cancer drugs specifically targeting the invasive or metastatic phenotype of tumour cells.
We propose to validate at the preclinical level a strategy that targets the critical mechanism allowing apoptosis evasion and survival of invasive or metastatic tumour cells. Anoikis is a process by which a cell detached from its resident tissue undergoes apoptosis as a result of loss of normal cell-matrix interactions. Loss of anoikis allows survival of cancer cells in abnormal microenvironments, such as tissue compartments invaded by the primary tumour, and the intravascular compartment during the metastatic process. Participant 2 has recently discovered that the BDNF receptor TrkB is a potent suppressor of anoikis and is responsible for apoptosis evasion that occurs in aggressive human tumours overexpressing TrkB (Douma et al., 2004). The aim of the present proposal is to validate TrkB as a target for new anticancer drugs, aiming to restore anoikis and thereby destroy the invasive and metastatic cancer cells. This validation will include the identification TrkB-expressing tumour cell lines amongst a collection of resected human cancers. Then, abrogation of TrkB mediated signalling will be achieved by either selective TrkB mRNA-targeting small interfering RNAs (RNAi) delivered by viral vectors, or by novel and potent small molecule inhibitors that will be designed and synthesized.
The efficacy of these tools will be assessed by using anoikis-sensitive cell models and xenograft mouse models, particularly orthotopic metastasis models derived from human tumours. The mechanisms of TrkB-dependent anoikis suppression will also be investigated in order to identify additional markers for invasive and metastatic capability and novel drug target
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
- natural sciences biological sciences genetics RNA
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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.
FP6-2005-LIFESCIHEALTH-6
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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
BOULOGNE
France
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.