Enhancing radiotherapy through a greater understanding of homologous recombination.
Enhancing radiotherapy through a greater understanding of homologous recombination.
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DOI：
10.1016/j.semradonc.2010.05.001
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发表时间：
2010-10
影响因子：
3.5
通讯作者：
Powell SN
中科院分区：
文献类型：
--
作者：
Barker CA;Powell SN
用于治疗癌症的放射疗法可引起广泛的细胞效应，其中最具生物学效力的是 DNA 中的双链断裂。修复 DNA 双链断裂的过程涉及两种主要机制之一：非同源末端连接或同源重组。在这篇综述中，我们回顾了同源重组的分子机制，特别是它与修复电离辐射造成的 DNA 损伤有关。我们还介绍了同源重组在人类癌症中可能出现功能障碍的具体情况，以及如何识别这种功能异常。我们还讨论了基于 DNA 修复途径各个步骤中同源重组缺陷可利用的治疗机会。在这些潜在的治疗机会的同时，我们回顾了当代的临床试验，其中利用放射治疗与生物靶向药物相结合可以增强利用同源重组中这些缺陷的策略。我们的结论是，放射肿瘤学领域仅仅触及了潜在高效治疗策略的表面。
Radiotherapy for the treatment of cancer can cause a wide range of cellular effects, the most biologically potent of which is the double strand break in DNA. The process of repairing DNA double strand breaks involves one of two major mechanisms: non-homologous end-joining or homologous recombination. In this review, we review the molecular mechanisms of homologous recombination, in particular as it relates to the repair of DNA damage from ionizing radiation. We also present specific situations where homologous recombination may be dysfunctional in human cancers, and how this functional abnormality can be recognized. We also discuss the therapeutic opportunities that can be exploited based on deficiencies in homologous recombination at various steps in the DNA repair pathway. Side-by-side with these potential therapeutic opportunities, we review the contemporary clinical trials in which strategies to exploit these defects in homologous recombination can be enhanced by the use of radiotherapy in conjunction with biologically-targeted agents. We conclude that the field of radiation oncology has only scratched the surface of a potentially highly efficacious therapeutic strategy.