Topoisomerase I poisons-induced autophagy: Cytoprotective, Cytotoxic or Non-protective.
Topoisomerase I poisons-induced autophagy: Cytoprotective, Cytotoxic or Non-protective.
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DOI：
10.1080/27694127.2022.2155904
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发表时间：
2023-01-01
期刊：
影响因子：
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通讯作者：
Gewirtz, David A
中科院分区：
文献类型：
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作者：
Elshazly, Ahmed M;Wright, Polina A;Gewirtz, David A
拓扑异构酶 I 抑制剂是一类广泛使用的抗肿瘤药物，可促进肿瘤细胞 DNA 的单链和双链断裂，从而导致肿瘤细胞死亡。拓扑替康和伊立替康是母体药物喜树碱的临床相关衍生物。与许多（如果不是大多数）抗癌药物的情况一样，伊立替康和拓扑替康促进自噬。然而，自噬是否具有细胞毒性、细胞保护性或非保护性尚不清楚，并且可能在很大程度上取决于所研究的肿瘤细胞的遗传背景。本综述探讨了有关临床前肿瘤模型中这些临床使用的拓扑异构酶 I 抑制剂诱导的自噬性质的现有文献，目的是确定自噬靶向是否有可能作为增强抗肿瘤反应和/或克服耐药性的治疗策略。
Topoisomerase I inhibitors represent a widely used class of antineoplastic agents that promote both single-stranded and double-stranded breaks in the DNA of tumor cells, leading to tumor cell death. Topotecan and irinotecan are the clinically relevant derivatives of the parent drug, camptothecin. As is the case with many if not most anticancer agents, irinotecan and topotecan promote autophagy. However, whether the autophagy is cytotoxic, cytoprotective, or non-protective is not clearly defined, and may depend largely upon the genetic background of the tumor cell being investigated. This review explores the available literature regarding the nature of the autophagy induced by these clinically utilized topoisomerase I inhibitors in preclinical tumor models with the goal of determining whether the targeting of autophagy might have potential as a therapeutic strategy to enhance the antitumor response and/or overcome drug resistance.