Project description
Insight into the blood-tumour barrier for improved glioblastoma therapy
The protective blood–brain barrier (BBB) tightly controls the passage of substances from the circulation into the brain. In brain tumours such as glioblastoma, the BBB is modified and is called the blood–tumour barrier (BTB). Funded by the Marie Skłodowska-Curie Actions programme, the GBM4EPI project aims to shed light into the BTB of glioblastoma, given its extremely poor survival. Researchers propose to develop glioblastoma BTB models that reproduce the temporal and dynamic status of blood flow as well as the varying degree of glioblastoma chemoresistance. These models will serve as a platform for testing various anticancer therapeutics, enhancing our understanding of BTB function and how it can be harnessed for improved glioblastoma clinical outcome.
Objective
"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."
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- medical and health sciencesclinical medicineoncology
- medical and health sciencesmedical biotechnologycells technologies
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Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
10124 Torino
Italy