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GBM are considered by the WHO classification as a single histological entity. However, considerable variability in biologic behavior still exits within this entity, resulting in significant differences in terms of prognosis and response to treatment. In an attempt to better understand GBM, many groups have used high-scale molecular profiling studies. These studies have revealed different molecular GBM subtypes. Interestingly, these different subtypes show different prognosis and respond differently to intensive therapy. Furthermore, data in the literature suggest that the high resistance of GBM to adjuvant therapy is partly due to the presence of a tumorigenic subpopulation of cancer stem cells called glioma stem cells (GSC). This is why, in complement to the 1st research subject, we also study the two following aspects: (1) Molecular classification of glioblastomas. We are currently trying to approach the molecular classification of GBM by the use of immunohistochemistry (IHC), a method which is easily applicable on a routine basis. This method has allow us so far to distinguish two clinically relevant classes of GBM based on the analysis of only three biomarkers (EGFR, p53 and PDGFRA) using image analysis to quantify their expression. We are currently investigating the possibility to improve this classification with the addition of other biomarkers resulting from our different research subjects in neuro-oncology. (2) Characterization of cancer stem cells in GBM. The cancer stem cell hypothesis suggests that only a distinct population of tumor cells, so-called cancer stem cells (CSC), is able to give rise to malignancies and tumor growth. CSC are defined as tumor cells with stem cell properties (i.e. asymmetric cell division, infinite growth, multipotency and cancer-initiating ability upon orthotopic implantation). A therapy will ultimately fail if it does not eliminate CSC; thus efficacy of a therapeutic agent depends on its efficacy against CSC. No specific marker of glioma stem cells (GSC) is currently reported in literature. Several markers are used to isolate GSC from human GBM but their expression is heterogeneous. This point complicates the accurate identification of GSC within GBM, an essential step to develop targeted therapies against GSC. Our project proposes to better characterize human GSC by studying the expression of several markers.
• F.R.S.-FNRS et Fonds associés (hors FRIA)
• Fonds spéciaux de recherche
• Région wallonne
• Autres fonds publics belges