Dr. Fortin – Subvention de recherche 2012

Dr. David Fortin, Universite de Sherbrooke, Sherbrooke, Quebec

Project Title: « Characterization of the chemoresistance profiles of malignant gliomas – A step towards individualized treatments »

What does the title mean?

This research focuses on the cells responsible for blocking treatment to the brain, specifically multi-drug resistant glioblastoma multiforme

Project Summary:

Dr FortinGlioblastoma multiforme (GBM) is the most frequent primary brain tumour. The incurability of this disease can partially be explained a chemoresistance phenomenon.

ABC transporter proteins are pumps expressed by glial cancer cells and by endothelial cell at the blood-brain barrier and blood-tumour barrier (BTB). In non-pathological conditions they protect the brain from drugs by insuring their exclusion from the brain, by pumping drugs back in the blood. However, these pumps are often overexpressed in cancer cells and give rise to chemoresistance to multiple anti-cancer drugs.

Research efforts to find specific inhibitors of theses transporters are currently in progress. Four members of this family of proteins have been identified to be express in malignant gliomas: MDR1, MRP1, MRP3, BCRP. Since the response to treatment is highly heterogeneous in GBM patients the search for novel biomarkers is crucial. The detailed characterization of the expression profile of ABC transporters could predict GBM progression and to allow the administration of a personalized treatment.

The aim of our research project is to characterize in glial cancer cells and BTB endothelial cells, the expression profile of four ABC transporters responsible for the drug delivery impediment to the brain and for the multidrug resistance in GBM patients.