Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Semin Radiat Oncol. 2010 Oct;20(4):241-9. doi: 10.1016/j.semradonc.2010.05.005.
Cellular DNA repair determines survival after ionizing radiation. Human tumors commonly exhibit aberrant DNA repair since they drive mutagenesis and chromosomal instability. Recent reports have shown alterations in the base excision repair (BER) and single strand break repair (SSBR) pathways in human tumors. Here we review these reports with respect to radiation sensitivity and the attempts to target such tumor-specific BER/SSBR aberrations. These aberrations can alter cellular resistance to therapeutic agents, including radiation. Some strategies therefore aim to counteract the radioresistance mediated by such aberrant DNA repair. Other strategies aim to exploit the dependence of the tumor, but not the normal cells, on backup repair mechanisms after radiation, therefore increasing the therapeutic window. Such tumor-targeted radiosensitization holds promise for increasing the efficacy of radiotherapy.
细胞 DNA 修复决定了电离辐射后的存活。由于人类肿瘤会驱动突变和染色体不稳定性，因此通常会出现异常的 DNA 修复。最近的报告显示，人类肿瘤中的碱基切除修复 (BER) 和单链断裂修复 (SSBR) 途径发生了改变。在这里，我们根据辐射敏感性以及针对此类肿瘤特异性 BER/SSBR 异常的尝试来回顾这些报告。这些异常会改变细胞对治疗剂（包括辐射）的抵抗力。因此，一些策略旨在抵消这种异常 DNA 修复介导的放射抗性。其他策略旨在利用肿瘤在辐射后对备用修复机制的依赖性，而不是正常细胞，从而增加治疗窗口。这种针对肿瘤的放射增敏作用有望提高放疗的疗效。
