Development of glioblastoma and blood-tumour barrier models for investigating th...
Development of glioblastoma and blood-tumour barrier models for investigating the combination therapy of anticancer agents and efflux pump inhibitors
"Glioblastoma (GBM) remains the most common malignant primary brain tumour with a median survival <2 years. One of the reasons for the failure of GBM therapy involves limited drug access to the tumour site due to the presence of t...
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Información proyecto GBM4EPI
Duración del proyecto: 23 meses
Fecha Inicio: 2025-01-01
Fecha Fin: 2026-12-31
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
"Glioblastoma (GBM) remains the most common malignant primary brain tumour with a median survival <2 years. One of the reasons for the failure of GBM therapy involves limited drug access to the tumour site due to the presence of the blood-brain barrier (BBB)/blood-tumour barrier (BTB). Although these barriers differ, they share some common features, such as tight junction (TJ) and efflux proteins of the ATP-binding (ABC) cassette superfamily that regulate drug access to the brain parenchyma. Similarly, efflux proteins have been identified in GBM that form an additional barrier. In the proposed research, five-dimensional (5D) models of GBM-BTB will take into account all characteristics essential to approach more realistic in vivo conditions, mainly the integration of glioblastoma stem cell (GSC) derived pericytes into BTB, and the incorporation of varying degrees of tumour cell differentiation (from GCS to well differentiated cells) showing a different degree of intrinsic chemoresistance. Additionally, microfluidic models reproducing blood flow will add a temporal and dynamic dimension (""5D models""). Once the models are established and compared with static ones, the effect of anticancer therapy and efflux protein inhibitors (EPIs) will be verified in terms of TJ and ABC protein expression using qRT-PCR and confocal microscopy. The identified combination therapy of anticancer agents and EPIs will lead to validation in patient-derived GMB-BTB models with different molecular profiles and degrees of resistance, with the goal of personalised medicine. By working on this project, the researcher will gain valuable experience that is needed to address the challenges associated with the treatment of therapy-resistant tumours. In general, this project may provide a more realistic view of the potential effect of combination therapy under in vivo conditions. This could ultimately expand the treatment options for cancer patients and increase their chances of survival."