范可尼贫血:从遗传疾病到癌症关联的DNA修复通路探索与治疗展望  

Fanconi Anemia:Exploration of DNA Repair Pathways from Genetic Diseases to Cancer and Prospects for Treatment

作　　者：史晋宇 邢琳 刘世佳 吕文豪 张冰琰 徐立君 张亚芬[1] SHI Jinyu;XING Lin;LIU Shijia;LYU Wenhao;ZHANG Bingyan;XU Lijun;ZHANG Yafen(Department of Breast Surgery,Fifth Hospital of Shanxi Medical University,ShanxiProvincial People’s Hospital,Taiyuan 030000,China;The Fifth Clinical Medical School ofShanxi Medical University,Taiyuan 030000,China)

机构地区：[1]山西医科大学第五医院,山西省人民医院乳腺外科,太原030000 [2]山西医科大学第五临床医学院,太原030000

出　　处：《肿瘤防治研究》2024年第1期67-72,共6页Cancer Research on Prevention and Treatment

摘　　要：范可尼贫血(FA)是一种遗传性疾病,其特征包括骨髓衰竭、发育异常和易患癌症。这种疾病是由基因突变引起的,导致修复DNA链间交联(ICLs)异常。DNA损伤反应失调会导致基因组不稳定,增加突变率和致癌风险。FA通路是DNA损伤应答的重要组成部分,在DNA链间交联修复和基因组稳定性方面发挥着关键作用。任何一个编码FA蛋白的基因胚系突变都会导致FA。随着体细胞癌中FA基因表达异常的普遍发生和不断开展的FA通路激活与化疗耐药相关性的研究,FA通路与癌症之间的联系得到了进一步确认,并且基于FA通路基因缺陷的靶向治疗也在逐步开发和应用。本文综述了FA蛋白在ICLs修复、FA信号网络调节以及其在癌症发病和预后中的重要作用,并探讨了靶向FA途径的小分子抑制剂的潜在应用。Fanconi anemia(FA)is an inheritable disorder that presents with bone marrow failure,developmental anomalies,and an increased susceptibility to cancer.The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links(ICLs).The resultant dysregulation of the DNA damage response mechanism can induce genomic instability,thereby elevating the mutation rates and the likelihood of developing cancer.The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity.A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA.The prevalence of aberrant FA gene expression in somatic cancer,coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy,has solidified the correlation between the FA pathway and cancer.Consequently,targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented.This review critically examines the involvement of the FA protein in the repair of ICLs,the regulation of the FA signaling network,and its implications in cancer pathogenesis and prognosis.Additionally,it explores the potential utility of small-molecule inhibitors that target the FA pathway.

关 键 词：范可尼贫血通路 DNA损伤修复 癌症易感性 预后 靶向治疗 

分 类 号：R730.2[医药卫生—肿瘤]