The potential of PARP inhibitors in neuro-oncology.
The potential of PARP inhibitors in neuro-oncology.
复制标题
DOI：
10.2217/cns.12.13
复制
发表时间：
2012-09-01
期刊：
影响因子：
--
通讯作者：
Chalmers, Anthony J
中科院分区：
文献类型：
--
作者：
Carruthers, Ross;Chalmers, Anthony J
DNA损伤剂在脑肿瘤的治疗中起着不可或缺的作用。我们在理解癌细胞如何修复DNA损伤方面的最新进展使我们有可能考虑将DNA损伤反应的修饰作为一种可能克服放疗和化疗耐药性的方法。PARP抑制剂是有效但无毒的药物，可以抑制DNA单链断裂的修复，并增加放射治疗和烷化化疗药物(包括替莫唑胺)的细胞毒作用。PARP抑制剂在神经肿瘤学中有潜在的应用，因为越来越多的证据表明，它们的放射和化学增敏作用是肿瘤特异性的。这篇综述探讨了PARP抑制剂的作用机制，并在中枢神经系统肿瘤学的背景下描述了它们可能的放射和化学增敏机制。作者继续回顾了他们在最近的临床试验中的发展，重点是胶质母细胞瘤。
DNA damaging agents have an integral role in the treatment of brain tumors. Recent advances in our understanding of how cancer cells repair DNA damage have made it possible to consider modification of the DNA damage response as a way in which resistance to radiotherapy and chemotherapy might be overcome. PARP inhibitors are potent but nontoxic drugs that inhibit repair of DNA single-strand breaks and increase the cytotoxic effects of radiotherapy and alkylating chemotherapy agents, including temozolomide. PARP inhibitors have potential applications in neuro-oncology because there is increasing evidence that their radio- and chemo-sensitizing effects are tumor specific. This review explores the mechanisms of action of PARP inhibitors and describes their putative mechanisms of radio- and chemo-sensitization in the context of CNS oncology. The authors go on to review their development in recent clinical trials, with a focus on glioblastoma.