Communication Dans Un Congrès Année : 2018

O 086: Radiosensitization Effect of Talazoparib, a PARP inhibitor, on Glioblastoma Stem Cells Exposed to X-rays and Carbon Ions

Résumé

Glioblastoma, the most common and deadly glioma subtype in adults, is a radioresistant tumor. Despite continuous improvements in treatment, 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 have recently emerged as potential radiosensitizing agents. In this study, we investigated the preclinical efficacy of talazoparib, a new PARP inhibitor, in association with low linear energy transfer (LET) and high 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 (Stupp combination). The use of PARP inhibitors combined with carbon beam irradiation drastically reduced the GSC frequency of GBM cell lines in vitro. In particular, talazoparib combined with photonic irradiation induced a marked and prolonged G2/M block, whereas talazoparib combined with 2-Gy carbon irradiation reduced the GSC fraction by up to 98%. These results show that talazoparib is a new candidate that effects radiosensitization in radioresistant GSCs, and its combination with high LET particle therapy is promising.

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Dates et versions

hal-05459808 , version 1 (15-01-2026)

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  • HAL Id : hal-05459808 , version 1

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Y Saintigny, P Lesueur, E El-Habr, MP Junier, H Chneiweiss, et al.. O 086: Radiosensitization Effect of Talazoparib, a PARP inhibitor, on Glioblastoma Stem Cells Exposed to X-rays and Carbon Ions. 57th Annual Meeting of the Particle Therapy Cooperative Group, May 2018, Cincinnati (Ohio, USA), United States. ⟨hal-05459808⟩
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