Academic Journal

Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma: Efficacy and Protein Biomarkers of Resistance in Preclinical Models

التفاصيل البيبلوغرافية
العنوان: Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma: Efficacy and Protein Biomarkers of Resistance in Preclinical Models
المؤلفون: Julian Biau, Emmanuel Chautard, Nathalie Berthault, Leanne de Koning, Frank Court, Bruno Pereira, Pierre Verrelle, Marie Dutreix
المصدر: Frontiers in Oncology, Vol 9 (2019)
بيانات النشر: Frontiers Media S.A., 2019.
سنة النشر: 2019
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: radiation therapy, high grade glioma, Dbait, preclinical study, double-strand break, single-strand break, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: High grade glioma relapses occur often within the irradiated volume mostly due to a high resistance to radiation therapy (RT). Dbait (which stands for DNA strand break bait) molecules mimic DSBs and trap DNA repair proteins, thereby inhibiting repair of DNA damage induced by RT. Here we evaluate the potential of Dbait to sensitize high grade glioma to RT. First, we demonstrated the radiosensitizer properties of Dbait in 6/9 tested cell lines. Then, we performed animal studies using six cell derived xenograft and five patient derived xenograft models, to show the clinical potential and applicability of combined Dbait+RT treatment for human high grade glioma. Using a RPPA approach, we showed that Phospho-H2AX/H2AX and Phospho-NBS1/NBS1 were predictive of Dbait efficacy in xenograft models. Our results provide the preclinical proof of concept that combining RT with Dbait inhibition of DNA repair could be of benefit to patients with high grade glioma.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2234-943X
Relation: https://www.frontiersin.org/article/10.3389/fonc.2019.00549/full; https://doaj.org/toc/2234-943X
DOI: 10.3389/fonc.2019.00549
URL الوصول: https://doaj.org/article/8fa16a5c8e64471d98e369ff7925be88
رقم الانضمام: edsdoj.8fa16a5c8e64471d98e369ff7925be88
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2234943X
DOI:10.3389/fonc.2019.00549