The Reciprocal Interaction of Small Molecule Protein Kinase Inhibitors and ATP-Binding Cassette Transporters in Targeted Cancer Therapy
The Reciprocal Interaction of Small Molecule Protein Kinase Inhibitors and ATP-Binding Cassette Transporters in Targeted Cancer Therapy
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小分子蛋白激酶抑制剂和 ATP 结合盒转运蛋白在靶向癌症治疗中的相互作用
DOI：
10.6000/1929-2279.2013.02.01.8
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Xin Wang
中科院分区：
文献类型：
--
作者：
Hong-Ye Zhao;Hongjiang Wei;Xin Wang
蛋白激酶已成为仅次于G蛋白偶联受体的第二大药物靶点。目前，15种小分子蛋白激酶抑制剂（PKIs）已获得食品和药物管理局（FDA）批准用于癌症治疗。然而，在这些小分子PKIs的临床使用过程中，耐药性已成为反复出现的问题。它们的治疗潜力取决于其细胞内靶点的进入，而这些靶点受某些膜ATP结合盒（ABC）转运蛋白的显著影响。ABC转运蛋白是临床多重耐药（MDR）的主要原因，并可能导致癌症患者对PKI产生耐药性。某些PKIs可调节ABC转运体的活性，影响自身及其他化学性质无关药物的代谢。此外，最近有报道说，一些PKIs可以调节ABC转运蛋白在肿瘤细胞中的表达，从而影响其在细胞内的积累和抗肿瘤疗效。在这篇综述中，总结了具有临床意义的PKIs与MDR相关ABC转运蛋白，特别是ABCB 1和ABCG 2的相互作用。关键词：蛋白激酶抑制剂，ABC转运蛋白，P-gp/ABCB 1，BCRP/ABCG 2，靶向肿瘤治疗。
Protein kinases have become the second most important group of drug targets, after G-protein-coupled receptors. Currently, 15 small molecule protein kinase inhibitors (PKIs) have received food and drug administrator (FDA) approval to be used as cancer treatments. However, in the course of clinical use of these small molecule PKIs, drug resistance has become a recurring problem. Their therapeutic potential depends on access to their intracellular targets, which significantly affected by certain membrane ATP-binding cassette (ABC) transporters. ABC transporters were major causes of clinical multiple drug resistance (MDR) and might be resulting in the development of resistance to PKIs in cancer patients. Some PKIs could modulate the activity of ABC transporters and affect the metabolism of themselves and other chemically unrelated drugs. Moreover, it has been recently reported that some PKIs could regulate the expression of ABC transporters in tumor cells, thereby affect their intracellular accumulation and antitumor efficacy. In this review, the reciprocal interaction of clinically important PKIs with the MDR-related ABC transporters, in particular ABCB1 and ABCG2, was summarized. Keyword: Protein Kinase Inhibitors, ABC Transporters, P-gp/ABCB1, BCRP/ABCG2, Targeted Cancer Therapy.
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影响因子：
3.7
作者：
Martin J;Anamika K;Srinivasan N
通讯作者：
Srinivasan N
影响因子：
11.2
作者：
Dai CL;Tiwari AK;Wu CP;Su XD;Wang SR;Liu DG;Ashby CR Jr;Huang Y;Robey RW;Liang YJ;Chen LM;Shi CJ;Ambudkar SV;Chen ZS;Fu LW
通讯作者：
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DOI：
10.1056/nejmoa1002028
发表时间：
2010-09-16
期刊：
The New England journal of medicine
影响因子：
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作者：
Verstovsek S;Kantarjian H;Mesa RA;Pardanani AD;Cortes-Franco J;Thomas DA;Estrov Z;Fridman JS;Bradley EC;Erickson-Viitanen S;Vaddi K;Levy R;Tefferi A
通讯作者：
Tefferi A
影响因子：
5.3
作者：
Usuda, J.;Ohira, T.;Kato, H.
通讯作者：
Kato, H.
DOI：
10.4137/cmo.s4259
发表时间：
2011
期刊：
Clinical Medicine Insights. Oncology
影响因子：
--
作者：
Ksienski D
通讯作者：
Ksienski D