Zhu Yongjian, Hu Jue, Hu Yiduo, Liu Weiguo
Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Cancer Treat Rev. 2009 Nov;35(7):590-6. doi: 10.1016/j.ctrv.2009.06.005. Epub 2009 Jul 26.
Increased chemo-resistance and radio-resistance of cancer cells is a major obstacle in the treatment and management of malignant cancers. An important mechanism that underlies the development of such therapeutic resistance is that cancer cells recognize DNA lesions induced by DNA-damaging agents and by ionizing radiation, and repair these lesions by activating various DNA repair pathways. Therefore, Use of pharmacological agents that can inhibit certain DNA repair pathways in cancer cells has the potential for enhancing the targeted cytotoxicity of anticancer treatments and reversing the associated therapeutic resistance associated with DNA repair; such agents, offering a promising opportunity to achieve better therapeutic efficacy. Here we review the major DNA repair pathways and discuss recent advances in the development of novel inhibitors of DNA repair pathways; many of these agents are under preclinical/clinical investigation.
癌细胞化疗耐药性和放疗耐药性的增加是恶性肿瘤治疗和管理中的主要障碍。这种治疗耐药性产生的一个重要机制是癌细胞识别由DNA损伤剂和电离辐射诱导的DNA损伤，并通过激活各种DNA修复途径来修复这些损伤。因此，使用能够抑制癌细胞中某些DNA修复途径的药物有可能增强抗癌治疗的靶向细胞毒性，并逆转与DNA修复相关的治疗耐药性；这类药物为实现更好的治疗效果提供了一个有前景的机会。在此，我们综述主要的DNA修复途径，并讨论DNA修复途径新型抑制剂开发的最新进展；其中许多药物正处于临床前/临床研究阶段。
