Department of Neurosciences, Moores UCSD Cancer Center, University of California, San Diego, CA, USA.
Future Oncol. 2011 Nov;7(11):1335-46. doi: 10.2217/fon.11.111.
The incorporation of radiotherapy into multimodality treatment plans has led to significant improvements in glioma patient survival. However, local recurrence from glioma resistance to ionizing radiation remains a therapeutic challenge. The tumoricidal effect of radiation therapy is largely attributed to the induction of dsDNA breaks (DSBs). In the past decade, there have been tremendous strides in understanding the molecular mechanisms underlying DSB repair. The identification of gene products required for DSB repair has provided novel therapeutic targets. Recent studies revealed that many US FDA-approved cancer agents inhibit DSB repair by interacting with repair proteins. This article will aim to provide discussion of DSB repair mechanisms to provide molecular targets for radiation sensitization of gliomas and a discussion of FDA-approved cancer therapies that modulate DSB repair to highlight opportunities for combination therapy with radiotherapy for glioma therapy.
放射治疗纳入多模态治疗方案显著改善了脑胶质瘤患者的生存。然而，脑胶质瘤对电离辐射的抵抗导致局部复发仍然是一个治疗挑战。放射治疗的肿瘤杀伤作用主要归因于双链 DNA 断裂（DSBs）的诱导。在过去的十年中，人们在理解 DSB 修复的分子机制方面取得了巨大进展。鉴定 DSB 修复所需的基因产物为提供了新的治疗靶点。最近的研究表明，许多美国食品和药物管理局批准的癌症药物通过与修复蛋白相互作用来抑制 DSB 修复。本文旨在讨论 DSB 修复机制，为脑胶质瘤的放射增敏提供分子靶点，并讨论美国食品和药物管理局批准的癌症治疗药物调节 DSB 修复，以突出与放射治疗联合治疗脑胶质瘤的机会。
