Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Future Oncol. 2014 May;10(7):1215-37. doi: 10.2217/fon.14.60.
Disruptions in DNA repair pathways predispose cells to accumulating DNA damage. A growing body of evidence indicates that tumors accumulate progressively more mutations in DNA repair proteins as cancers progress. DNA repair mechanisms greatly affect the response to cytotoxic treatments, so understanding those mechanisms and finding ways to turn dysregulated repair processes against themselves to induce tumor death is the goal of all DNA repair inhibition efforts. Inhibition may be direct or indirect. This burgeoning field of research is replete with promise and challenge, as more intricacies of each repair pathway are discovered. In an era of increasing concern about healthcare costs, use of DNA repair inhibitors can prove to be highly effective stewardship of R&D resources and patient expenses.
DNA 修复途径的中断使细胞容易积累 DNA 损伤。越来越多的证据表明,随着癌症的进展,肿瘤在 DNA 修复蛋白中积累的突变逐渐增多。DNA 修复机制极大地影响了对细胞毒性治疗的反应,因此了解这些机制并找到方法使失调的修复过程对自身产生作用,以诱导肿瘤死亡,是所有 DNA 修复抑制努力的目标。抑制可以是直接的,也可以是间接的。随着对每条修复途径的更多复杂性的发现,这个迅速发展的研究领域充满了希望和挑战。在人们越来越关注医疗保健成本的时代,使用 DNA 修复抑制剂可以被证明是对研发资源和患者费用的高度有效的管理。