In vitro effect of ionizing radiation on primary glioblastoma cells as a basis for multitarget therapy

Abstract

Glioblastoma is the most common primary brain tumor. It is highly refractory to therapeutic intervention and the mean patient survival is only 15 months, despite maximal aggressive treatment. Radiotherapy is the most important postoperative treatment and the combinatory effect of new pharmacological therapies in combination with radiotherapy is of interest. In this work we examined the effect of radiotherapy on differentiated glioblastoma tumor cells, and characterized them in terms of radiobiologic parameters. Further, we examined the differences between single-dose irradiation (SD-IR) and clinically relevant fractionated dose radiation (FD-IR). Because of the repetitive activation of DNA damage response after FD-IR, SD-IR is not a good surrogate marker for FD-IR. In a next step we integrated irradiation into a combination therapy approach, consisting of pharmacological inhibition of PI3K in combination with chemotherapy.