Repair of DNA double-strand breaks (DSBs) and its regulation are tightly integrated inside cells. Homologous recombination, nonhomologous end joining and microhomology mediated end joining are three major DSB repair pathways in mammalian cells. Targeting proteins associated with these repair pathways using small molecule inhibitors can prove effective in tumors, especially those with deregulated repair. Sensitization of cancer to current age therapy including radio and chemotherapy, using small molecule inhibitors is promising and warrant further development. Although several are under clinical trial, till date no repair inhibitor is approved for commercial use in cancer patients, with the exception of PARP inhibitors targeting single-strand break repair. Based on molecular profiling of repair proteins, better prognostic and therapeutic output can be achieved in patients. In the present review, we highlight the different mechanisms of DSB repair, chromatin dynamics to provide repair accessibility and modulation of inhibitors in association with molecular profiling and current gold standard treatment modalities for cancer.

DNA 双链断裂 (DSB) 的修复及其调节在细胞内紧密整合。同源重组、非同源末端连接和微同源介导的末端连接是哺乳动物细胞中三种主要的 DSB 修复途径。使用小分子抑制剂靶向与这些修复途径相关的蛋白质可以证明对肿瘤有效，尤其是那些修复失调的肿瘤。使用小分子抑制剂使癌症对当前年龄疗法（包括放射和化学疗法）敏感是有希望的，并且值得进一步发展。尽管有几个正在进行临床试验，但迄今为止，除了针对单链断裂修复的 PARP 抑制剂外，还没有任何修复抑制剂被批准用于癌症患者的商业用途。基于修复蛋白的分子分析，患者可以获得更好的预后和治疗效果。在本综述中，我们重点介绍了 DSB 修复的不同机制、染色质动力学，以提供修复可及性和抑制剂的调节，以及分子谱分析和当前癌症的金标准治疗方式。