ADAR1与肿瘤铂类耐药：从机制解析到靶向干预的研究回顾

曹 双双1, 张 星宇1, 可 秀1, 代 雅婷1, 郝晓 婷*2
1、湖北医药学院药护学院第四临床学院
2、湖北医药学院附属襄阳市第一人民医院

摘要


铂类药物是临床应用广泛的化疗药物，但其疗效常因肿瘤细胞产生耐药性而受限。耐药机制复杂，涉及药物代谢、DNA损伤修复增强及凋亡逃逸等多方面。近年来研究发现，由ADAR1介导的异常A-to-I RNA编辑被发现与肿瘤发生增加及多种癌症中化疗耐药性的发展有关。本文系统综述铂类药物的经典耐药机制，重点阐述ADAR1在介导耐药中的核心作用，并总结靶向ADAR1以逆转耐药的最新策略，为深入理解铂类耐药机制及开发新型治疗提供参考。

关键词


ADAR1；RNA编辑；铂类耐药；DNA损伤修复；靶向治疗

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参考


[1]谭书想.常见铂类抗肿瘤药物耐药机制和不良反应的比较分析[J].中南药学，2015，13（05）：517-520.

[2]王冬博，聂晶，武慧娜，等.铂类抗肿瘤药物耐药机制的研究进展和应对策略[J].药学实践杂志，2022，40（04）：302-308.

[3]胡倩倩，王振辉，牛超，等.铂类抗肿瘤药物耐药机制研究进展[J].药学进展，2017，41（10）：769-774.

[4]王松，李积德，赵君慧，等.铂类化疗药物的耐药机制[J].医药前沿，2011，1（24）：189-190.

[5]姜韬，梁军.切除修复交叉互补基因1与铂类药物耐药[J].国际肿瘤学杂志，2008，35（12）：885-888.

[6]Bass BL, Nishikura K, Keller W,et al. A standardized nomenclature for adenosine deaminases that act on RNA[J]. RNA. 1997 Sep;3(9):947-9.

[7]PAZ N, LEVANON E Y, AMARIGLIO N, et al. Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade [J]. Nature, 2019, 565 (7738): 43-48.

[8]Ashani K, L B B. Mechanistic insights into editing-site specificity of ADARs.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(48): E3295-304.

[9]Higuchi M, Single FN, Köhler M, et al. RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency[J]. Cell. 1993 Dec 31;75(7):1361-70.

[10]WAGNER R W, SMITH J E, COOPERMAN B S, et al. A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs [J]. Proceedings of the National Academy of Sciences, 1989, 86 (8): 2647-2651.

[11]Patterson JB, Samuel CE. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase[J]. Mol Cell Biol. 1995 Oct;15(10):5376-88.

[12]Yang W, Chendrimada TP, Wang Q, et al. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases[J]. Nat Struct Mol Biol. 2006 Jan;13(1):13-21.

[13]THORP E B, MANLEY G T. RNA editing in cancer: a new frontier in precision oncology [J]. Nature Reviews Cancer, 2020, 20 (12): 711-726.

[14]Liu Q, Huang CS, Chen S, et al. ADAR1 promotes cisplatin resistance in intrahepatic cholangiocarcinoma by regulating BRCA2 expression through A-to-I editing manner[J]. Cell Prolif. 2024 Oct;57(10):e13659.

[15]Wang H, Yang L, Liu R, He H, et al. ADAR1 affects gastric cancer cell metastasis and reverses cisplatin resistance through AZIN1[J]. Anticancer Drugs. 2023 Nov 1;34(10):1132-1145.

[16]Wong TL, Loh JJ, Lu S, et al. ADAR1-mediated RNA editing of SCD1 drives drug resistance and self-renewal in gastric cancer[J]. Nat Commun. 2023 May 19;14(1):2861.

[17]Umeda H, Shigeyasu K, Takahashi T, et al. ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer[J]. Mol Cancer.2025 Apr 16;24(1):116.

[18]Zhu Y, Shen H, Ding J, et al. Design, Synthesis, and Activity Evaluation of Novel Nucleosides as ADAR1 Inhibitor for the Treatment of Prostate Cancer[J]. J Med Chem. 2025;68(14):14495-14513.

[19]Wu F, Qian Y, Ge C, et al. Oxygen/siRNA-carrying fluoro-nanosensitizers for radio-immunotherapy sensitization[J]. Acta Biomater. 2025;196:423-435.

[20]Umeda H, Shigeyasu K, Takahashi T, et al. ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer[J]. Mol Cancer. 2025;24(1):116. Published 2025 Apr 16.


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