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Content archived on 2024-06-18

Identification of TRAIL sensitivity/resistance mechanisms and searching for novel TRAIL-sensitizing agents in Glioblastoma Multiforme

Objective

The overall goal of this proposal is to explore the molecular basis of TRAIL-response in an aggressive brain cancer, Glioblastoma Multiforme (GBM), and identify new reagents that will augment the TRAIL response of GBMs. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL), emerged as a prime candidate for cancer treatment due to its tumor-specificity, however its clinical success is likely limited by the innate or acquired resistance of some tumors to TRAIL. Dr. Bagci-Onder will address whether aberrant expression or activity of apoptotic program components is associated with TRAIL-resistance in GBMs. Specifically, she will address the role of a pro-apoptotic factor, harakiri (HRK), that she found to be significantly repressed in the TRAIL-resistant subpopulation of a primary GBM cell line. The potential role of this hitherto unstudied protein in GBM cell TRAIL response will be uncovered using expression analysis and functional assays in a large panel of GBM lines with varying TRAIL responses. Since multiple components of TRAIL signaling might be misregulated in TRAIL-resistant cells, Dr. Bagci-Onder will generate dual bioluminescent reporter systems of HRK and other TRAIL-associated factors, such as TRAIL receptors DR4/DR5; TRAIL signaling inhibitor proteins Flip, XIAP and Bcl-2 to assess gene expression changes. It is becoming evident that TRAIL-based combinatorial therapies with additional agents that can augment the TRAIL-response of tumors are more efficacious than using TRAIL alone. Using the novel reporter systems, Dr. Bagci-Onder will screen for novel TRAIL-sensitizing agents to identify potential TRAIL-sensitizers among FDA-approved chemicals. The function of these agents will be validated in mouse xenograft GBM models using neural stem cells as vehicles for TRAIL delivery. Together, this project will further the understanding of GBM biology and lead to potential clinical applications.

Fields of science (EuroSciVoc)

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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.

Call for proposal

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FP7-PEOPLE-2013-CIG
See other projects for this call

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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

KOC UNIVERSITY
EU contribution
€ 100 000,00
Address
RUMELI FENERI YOLU SARIYER
34450 Istanbul
Türkiye

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Region
İstanbul İstanbul İstanbul
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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