Protease-activated receptor 1 (PAR1): a promising target for the treatment of glioblastoma?

Glioblastoma (GBM), the highest grade astrocytoma, presents as a very aggressive cancer with poor prognosis. Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor that elicits several pro-tumoral responses. The expression levels of PAR1 are positively correlated with the histological grade of malignancy in astrocytomas. PAR1 expression correlates with increased VEGF expression levels and decreased survival in GBM patients. Analysis of PAR1 expression in human tissue samples of GBM showed strong correlation between PAR1 expression and epidermal growth factor receptor (EGFR) amplification as well as CDKN2A and PTEN deletion, all hallmarks of the classical subtype. PAR1 has recently been identified as overexpressed in glioma tumor progenitor cells (TPCs). In this context, either genetic or pharmacological inhibition of PAR1 decreases the in-vitro aggressive properties of glioma TPCs. Remarkably, PAR1 knockdown in TPCs has significant impact upon in vivo tumor growth in mouse models. Overall, PAR1 emerges as a potential new target for the treatment of GBM.