Cancer cells show various types of mutations and aberrant expression in genes involved in DNA repair responses. These alterations induce genome instability and promote carcinogenesis steps and cancer progression processes. These defects in DNA repair have also been considered as suitable targets for cancer therapies. A most effective target so far clinically demonstrated is “homologous recombination repair defect”, such as BRCA1/2 mutations, shown to cause synthetic lethality with inhibitors of poly(ADP-ribose) polymerase (PARP), which in turn is involved in DNA repair as well as multiple physiological processes. Different approaches targeting genomic instability, including immune therapy targeting mismatch-repair deficiency, have also recently been demonstrated to be promising strategies. In these DNA repair targeting-strategies, common issues could be how to optimize treatment and suppress/conquer the development of drug resistance. In this article, we review the extending framework of DNA repair response pathways and the potential impact of exploiting those defects on cancer treatments, including chemotherapy, radiation therapy and immune therapy.

癌细胞在涉及DNA修复反应的基因中显示出各种类型的突变和异常表达。这些改变引起基因组不稳定并促进致癌步骤和癌症进展过程。DNA修复中的这些缺陷也被认为是癌症治疗的合适靶标。迄今为止，临床上证明的最有效的靶标是“同源重组修复缺陷”，例如BRCA1 / 2突变，证明与聚（ADP-核糖）聚合酶（PARP）抑制剂引起合成杀伤力，而后者又参与DNA修复以及多种生理过程。最近还证明了针对基因组不稳定的不同方法，包括针对错配修复缺陷的免疫疗法，是有前途的策略。在这些DNA修复靶向策略中，常见的问题可能是如何优化治疗并抑制/克服耐药性的发展。在本文中，我们回顾了DNA修复反应途径的扩展框架以及利用这些缺陷对癌症治疗（包括化学疗法，放射疗法和免疫疗法）的潜在影响。