Drug repurposing approach to identify and validate potential drug candidates in vitro for glioblastoma based on different molecular subtypes.

Abstract

[eng] Glioblastoma (GBM) is one of the most malignant types of central nervous system tumors with poor prognosis and lack of effective therapies. Recent high-throughput data revealed the existence of three different GBM molecular subtypes: Classical, Mesenchymal, and Proneural. To overcome the high costs associated with current methods for subtype classification, the Cancer Epigenetics Lab (EPIGEN Lab) at IdISBa has developed a more affordable classification method based on quantitative PCR (qPCR) analysis using a panel of 15 genes. Here, we have tested this qPCR-based method to classify several GBM cell lines in vitro. However, our results showed that the qPCR method was not able to match the subtype classification obtained from conventional methods based on transcriptomic analysis. This discrepancy was probably due to a lack of heterogeneity between the selected GBM cell lines selected, an anticipated limitation of the qPCR method. Based on transcriptomic analysis of GBM subtypes and Gene Set Enrichment Analysis, we generated a list of subtype-specific candidate drugs. Although at a very preliminary stage, our in vitro test of selected drugs showed some promising results on subtype specificity. These results are encouraging and highlight the relevance of GBM patient stratification based on their molecular subtype