Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, 06520, USA.
Institute of Cancer Sciences & Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK.
J Neurooncol. 2017 Sep;134(3):513-521. doi: 10.1007/s11060-017-2427-7. Epub 2017 Jul 31.
The finding that most GBMs recur either near or within the primary site after radiotherapy has fueled great interest in the development of radiosensitizers to enhance local control. Unfortunately, decades of clinical trials testing a wide range of novel therapeutic approaches have failed to yield any clinically viable radiosensitizers. However, many of the previous radiosensitizing strategies were not based on clear pre-clinical evidence, and in many cases blood-barrier penetration was not considered. Furthermore, DNA repair inhibitors have only recenly arrived in the clinic, and likely represent potent agents for glioma radiosensitization. Here, we present recent progress in the use of small molecule DNA damage response inhibitors as GBM radiosensitizers. In addition, we discuss the latest progress in targeting hypoxia and oxidative stress for GBM radiosensitization.
研究发现，大多数胶质母细胞瘤在放疗后要么在原发部位附近复发，要么就在原发部位内复发，这激发了人们开发放射增敏剂以提高局部控制率的极大兴趣。不幸的是，数十年来，临床试验测试了广泛的新治疗方法，但都没有产生任何可行的放射增敏剂。然而，许多以前的放射增敏策略并非基于明确的临床前证据，而且在许多情况下并未考虑血脑屏障的穿透性。此外，DNA 修复抑制剂最近才进入临床，可能是胶质母细胞瘤放射增敏的有效药物。在这里，我们介绍了小分子 DNA 损伤反应抑制剂作为 GBM 放射增敏剂的最新进展。此外，我们还讨论了针对胶质母细胞瘤放射增敏的缺氧和氧化应激的最新进展。
