Cancer

In vitro, patient sample, cell culture and rat studies identified an inhibitor of thrombin-mediated PAR1 activation that could help treat glioblastoma. In tumor samples from patients, PAR1 expression was higher than in matched normal tissue samples. Chemical synthesis of analogs of PAR1's N-terminal thrombin recognition site sequence and activity assays in a PAR1-expressing rat glioma cell line identified a chemically modified six amino acid peptide that inhibited secretion of the PAR1 activator thrombin with an IC₅₀ of 0.5 pM and decreased proliferation and colony formation compared with vehicle. In a rat model of glioblastoma, the compound decreased brain edema and increased survival. Next steps could include testing the compound in other models of glioblastoma...