Radiosensitization Effect of Talazoparib, a Parp Inhibitor, on Glioblastoma Stem Cells Exposed to Low and High Linear Energy Transfer Radiation

Scientific Reports
Paul LesueurYannick Saintigny

Abstract

Despite continuous improvements in treatment of glioblastoma, tumor recurrence and therapy resistance still occur in a high proportion of patients. One underlying reason for this radioresistance might be the presence of glioblastoma cancer stem cells (GSCs), which feature high DNA repair capability. PARP protein plays an important cellular role by detecting the presence of damaged DNA and then activating signaling pathways that promote appropriate cellular responses. Thus, PARP inhibitors (PARPi) have recently emerged as potential radiosensitizing agents. In this study, we investigated the preclinical efficacy of talazoparib, a new PARPi, in association with low and high linear energy transfer (LET) irradiation in two GSC cell lines. Reduction of GSC fraction, impact on cell proliferation, and cell cycle arrest were evaluated for each condition. All combinations were compared with a reference schedule: photonic irradiation combined with temozolomide. The use of PARPi combined with photon beam and even more carbon beam irradiation drastically reduced the GSC frequency of GBM cell lines in vitro. Furthermore, talazoparib combined with irradiation induced a marked and prolonged G2/M block, and decreased proliferation. These result...Continue Reading

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Methods Mentioned

BETA
biopsy
X-ray
flow cytometry
FCS
ubiquitination

Clinical Trials Mentioned

NCT03212742

Software Mentioned

GraphPad Prism®
XLSTAT
GraphPad
ELDA
Excel
DeNovo
FCS Express

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