Oxidatively induced DNA damage is caused in living organisms by endogenous and exogenous reactive species. DNA lesions resulting from this type of damage are mutagenic and cytotoxic and, if not repaired, can cause genetic instability that may lead to disease processes including carcinogenesis. Living organisms possess DNA repair mechanisms that include a variety of pathways to repair multiple DNA lesions. Mutations and polymorphisms also occur in DNA repair genes adversely affecting DNA repair systems. Cancer tissues overexpress DNA repair proteins and thus develop greater DNA repair capacity than normal tissues. Increased DNA repair in tumors that removes DNA lesions before they become toxic is a major mechanism for development of resistance to therapy, affecting patient survival. Accumulated evidence suggests that DNA repair capacity may be a predictive biomarker for patient response to therapy. Thus, knowledge of DNA protein expressions in normal and cancerous tissues may help predict and guide development of treatments and yield the best therapeutic response. DNA repair proteins constitute targets for inhibitors to overcome the resistance of tumors to therapy. Inhibitors of DNA repair for combination therapy or as single agents for monotherapy may help selectively kill tumors, potentially leading to personalized therapy. Numerous inhibitors have been developed and are being tested in clinical trials. The efficacy of some inhibitors in therapy has been demonstrated in patients. Further development of inhibitors of DNA repair proteins is globally underway to help eradicate cancer.

中文翻译：

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氧化诱导的DNA损伤及其在癌症中的修复。

氧化诱导的DNA损伤是由内源性和外源性反应物种在活生物体中引起的。由这种类型的损伤导致的DNA损伤是诱变的和细胞毒性的，如果不进行修复，可能会导致遗传不稳定，从而导致包括致癌在内的疾病过程。活生物体具有DNA修复机制，其中包括修复多种DNA损伤的多种途径。突变和多态性也发生在DNA修复基因中，对DNA修复系统产生不利影响。癌症组织过表达DNA修复蛋白，因此比正常组织具有更大的DNA修复能力。在肿瘤中消除DNA损伤之前增加其在肿瘤中的DNA修复水平，这是产生抗药性，影响患者生存的主要机制。积累的证据表明，DNA修复能力可能是患者对治疗反应的预测性生物标志物。因此，了解正常和癌性组织中DNA蛋白表达的知识可能有助于预测和指导治疗的发展，并产生最佳的治疗反应。DNA修复蛋白构成抑制剂的靶标，以克服肿瘤对治疗的抵抗力。用于联合治疗或作为单一治疗的单一药物的DNA修复抑制剂可能有助于选择性杀死肿瘤，可能导致个性化治疗。已经开发了许多抑制剂，并且正在临床试验中进行测试。已经在患者中证明了某些抑制剂在治疗中的功效。DNA修复蛋白抑制剂的进一步开发正在全球范围内进行，以帮助根除癌症。