Preclinical and clinical applications of enzastaurin in the treatment of malignant gliomas

Radiotherapy is essential in the treatment of malignant gliomas. However, it enhances the invasion of glioma cells and the secretion of vascular endothelial growth factor (VEGF) in experimental gliomas. We therefore assessed the combined effects of the protein kinase C inhibitor enzastaurin and radiotherapy in vitro and in vivo. The combination of enzastaurin and irradiation enhanced apoptosis in glioma cells in vitro. Basal and irradiation-induced secretion of VEGF were reduced by treatment with enzastaurin. Moreover, enzastaurin was not neurotoxic as assessed by the treatment of rat cerebellar granule neurons.…