Identifiering av signalvägar, målproteiner och nya terapier baserat på ursprungscellen för glioblastom
Tidsperiod: 2013-01-01 till 2015-12-31
Budget: 2 100 000 SEK
Our goal is to, based on cell of origin, stratify glioblastoma (GBM) into novel subclasses of clinical relevance, identify pathways and biomarkers of therapeutic value, and drugs with potency against glioma initiating cells (GICs). GBM is the most common primary malignant brain tumor with very poor prognosis and no cure. The cell of origin for GBM is unknown but most likely of glial lineage. GBM is maintained by a subset of cells called GICs that are more resistant to therapy making them an critical target for new treatments. Our hypothesis is that the cell of origin is an important factor to take into account in order to fully understand GBM development and we have solid results supporting this hypothesis, which show that the cell of origin is vital for the tumorigenic properties of experimental GICs. Here we will use a unique combination of mouse models of GBM targeting different cells of origin at specified times in development and with different oncogenic stimuli, isolate GICs and analyze their phenotypic properties and global gene expression to generate "cell of origin signatures". These will be compared to human GICs to stratify human GBM based on cell of origin. We will also use the "cell of origin signatures" to identify pathways/targets and screen for new anti-GBM drugs. This project has the potential to generate basic knowledge of GBM biology, identify better models for subtypes of GBM and discover new drugs effective against GICs.