Despite surgical resection and genotoxic treatment with ionizing radiation and the DNA alkylating agent temozolomide, glioblastoma remains one of the most lethal cancers, due in great part to the action of DNA repair mechanisms that drive resistance and tumor relapse. Understanding the molecular details of these mechanisms and identifying potential pharmacological targets have emerged as vital tasks to improve treatment. In this review, we introduce the various cellular systems and animal models that are used in studies of DNA repair in glioblastoma. We summarize recent progress in our knowledge of the pathways and factors involved in the removal of DNA lesions induced by ionizing radiation and temozolomide. We introduce the therapeutic strategies relying on DNA repair inhibitors that are currently being tested in vitro or in clinical trials, and present the challenges raised by drug delivery across the blood brain barrier as well as new opportunities in this field. Finally, we review the genetic and epigenetic alterations that help shape the DNA repair makeup of glioblastoma cells, and discuss their potential therapeutic impact and implications for personalized therapy.

中文翻译：

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DNA修复机制及其在胶质母细胞瘤中的临床影响。

尽管通过电离辐射和DNA烷基化剂替莫唑胺进行了手术切除和遗传毒性治疗，但胶质母细胞瘤仍是最致命的癌症之一，这在很大程度上归因于DNA修复机制的作用，该机制可促进耐药性和肿瘤复发。理解这些机制的分子细节并确定潜在的药理学目标已成为改善治疗的重要任务。在这篇综述中，我们介绍了胶质母细胞瘤DNA修复研究中使用的各种细胞系统和动物模型。我们总结了有关电离辐射和替莫唑胺引起的DNA损伤清除的途径和因素的最新进展。我们介绍了依赖于目前在体外或临床试验中测试的DNA修复抑制剂的治疗策略，并介绍了跨血脑屏障给药带来的挑战以及该领域的新机遇。最后，我们回顾了有助于塑造胶质母细胞瘤细胞DNA修复结构的遗传和表观遗传学改变，并讨论了它们对个体化治疗的潜在治疗作用和意义。