Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer Therapy.
Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer Therapy.
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DOI：
10.3390/biom5031652
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发表时间：
2015-07-22
期刊：
影响因子：
5.5
通讯作者：
Her C
中科院分区：
文献类型：
--
作者：
Xu Y;Her C
大多数化疗方案含有至少一种DNA损伤剂，优先影响癌细胞的生长。这种策略利用了正常细胞和癌细胞之间细胞增殖的差异。化疗药物通常被设计为靶向快速分裂的细胞，因为持续的增殖是癌症的共同特征[1，2]。快速DNA复制对于高度增殖的细胞是必不可少的，因此DNA复制的阻断将产生许多突变和/或染色体复制-最终触发细胞死亡[3]。沿着这些路线，DNA拓扑异构酶抑制剂是非常感兴趣的，因为它们有助于维持复制过程中拓扑异构酶产生的链断裂。在这篇文章中，我们讨论了拓扑异构酶（DNA）I（TOP 1）及其抑制剂的特点，以及潜在的DNA修复途径和TOP 1抑制剂在癌症治疗中的应用。
Most chemotherapy regimens contain at least one DNA-damaging agent that preferentially affects the growth of cancer cells. This strategy takes advantage of the differences in cell proliferation between normal and cancer cells. Chemotherapeutic drugs are usually designed to target rapid-dividing cells because sustained proliferation is a common feature of cancer [1,2]. Rapid DNA replication is essential for highly proliferative cells, thus blocking of DNA replication will create numerous mutations and/or chromosome rearrangements—ultimately triggering cell death [3]. Along these lines, DNA topoisomerase inhibitors are of great interest because they help to maintain strand breaks generated by topoisomerases during replication. In this article, we discuss the characteristics of topoisomerase (DNA) I (TOP1) and its inhibitors, as well as the underlying DNA repair pathways and the use of TOP1 inhibitors in cancer therapy.