Objective
Patients with aggressive brain cancer have a very poor prognosis with an average life expectancy of only ~12 to 17 months. High grade brain tumors are extremely difficult to treat due to tumor cell invasion, plus resistance of tumor cells to DNA-damaging therapy. This cellular aggressiveness within brain tumors has been attributed to a subpopulation of tumor cells that possess stem cells-like features.
Unlike differentiated tumor cells, brain tumour stem cells (BTSCs) possess the ability to self-renew, to withstand DNA-damaging therapy, and to give rise to new tumor mass. Therefore, targeting BTSCs is expected to improve the efficiency of anti-brain cancer therapy. In particular, targeting pathways that sustain the undifferentiated state of BTSCs is a novel strategy to treat aggressive brain tumors. However, this approach is hampered by a poor understanding of appropriate targets promoting the BTSC phenotype.
Recently, we have demonstrated that the adapter protein TRRAP maintains BTSCs in an undifferentiated and highly tumorigenic state. Consistently, elevated expression of TRRAP in human brain tumors has a strong negative effect on patient survival. Therefore, we aim to provide a basis toward the development of an effective therapeutic strategy against the malignant function of TRRAP in BTSCs.
To this end, we will use our established BTSC assay system and BTSC in vivo models in combination with differential proteomics to characterize TRRAP protein domains and TRRAP-protein interactions that critically promote the BTSC phenotype. Moreover, we will investigate the role of TRRAP during brain tumor invasion and potential additive effects between DNA-damaging therapy and inhibition of TRRAP function in vivo.
Overall, these interrelated approaches will validate TRRAP as a brain tumor target. Ultimately, we hope to reveal and exploit the Achilles’ heel of TRRAP-dependent tumorigenesis for developing a targeted therapeutic strategy against BTSC-driven brain tumors.
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 biochemistry biomolecules proteins proteomics
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
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Programme(s)
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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-2011-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
LS2 9JT Leeds
United Kingdom
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