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MRE11-RAD50-NBS1 复合物改变与 DNA 损伤反应:对癌症治疗的影响。

MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment.

机构信息

Department of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Mol Cancer. 2019 Nov 26;18(1):169. doi: 10.1186/s12943-019-1100-5.

Abstract

Genome instability is a hallmark of cancer cells and can be accelerated by defects in cellular responses to DNA damage. This feature of malignant cells opens new avenues for tumor targeted therapy. MRE11-RAD50-NBS1 complex plays a crucial role in sensing and repair of DNA damage. Through interacting with other important players of DNA damage response, MRE11-RAD50-NBS1 complex is engaged in various DNA damage repair pathways. Mutations in any member of this complex may lead to hypersensitivity to genotoxic agents and predisposition to malignancy. It is assumed that the defects in the complex may contribute to tumorigenesis and that treatments targeting the defect may be beneficial to cancer patients. Here, we summarized the recent research findings of the role of MRE11-RAD50-NBS1 complex in tumorigenesis, cancer treatment and discussed the potential approaches of targeting this complex to treat cancer.

摘要

基因组不稳定性是癌细胞的一个标志,其可通过细胞对 DNA 损伤反应的缺陷而加速。恶性细胞的这一特征为肿瘤靶向治疗开辟了新途径。MRE11-RAD50-NBS1 复合物在 DNA 损伤的感应和修复中发挥着关键作用。通过与 DNA 损伤反应的其他重要参与者相互作用,MRE11-RAD50-NBS1 复合物参与了各种 DNA 损伤修复途径。该复合物中任何成员的突变都可能导致对遗传毒性药物的敏感性增加和恶性肿瘤易感性增加。人们认为,该复合物的缺陷可能有助于肿瘤发生,针对该缺陷的治疗可能对癌症患者有益。在这里,我们总结了 MRE11-RAD50-NBS1 复合物在肿瘤发生、癌症治疗中的作用的最新研究发现,并讨论了靶向该复合物治疗癌症的潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c52/6878665/92f87d15f16a/12943_2019_1100_Fig1_HTML.jpg

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