Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up.
Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up.
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DOI：
10.2174/138161211797440186
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发表时间：
2011
影响因子：
3.1
通讯作者：
Bauer B
中科院分区：
文献类型：
--
作者：
Agarwal S;Hartz AM;Elmquist WF;Bauer B
脑癌是一种毁灭性的疾病。尽管有广泛的研究，脑肿瘤的治疗在很大程度上是无效的，脑癌的诊断仍然是致命的。脑癌治疗失败的部分原因可能是药物递送受限，受血脑和血肿瘤屏障、脑肿瘤细胞以及脑肿瘤干细胞样细胞中ABC药物外排转运蛋白P-gp和BCRP的影响。P-gp和BCRP限制各种抗癌药物进入脑和肿瘤组织，从而使化疗无效。为了克服这一障碍，已经提出了两种策略-靶向转运蛋白调节和直接转运蛋白抑制。在这篇评论中，我们将重点关注这些策略。我们首先介绍了可能下调P-gp和BCRP表达和/或转运活性的信号通路的最新发现。然后，我们详细强调了P-gp和BCRP在血脑屏障中作为“守门人合作团队”的新范式，讨论了其对脑癌治疗的影响，并总结了双重P-gp/BCRP抑制剂的最新研究结果。最后，我们提供了一个简短的总结与结论，并概述了未来的研究工作在这一领域的前景。
Brain cancer is a devastating disease. Despite extensive research, treatment of brain tumors has been largely ineffective and the diagnosis of brain cancer remains uniformly fatal. Failure of brain cancer treatment may be in part due to limitations in drug delivery, influenced by the ABC drug efflux transporters P-gp and BCRP at the blood-brain and blood-tumor barriers, in brain tumor cells, as well as in brain tumor stem-like cells. P-gp and BCRP limit various anti-cancer drugs from entering the brain and tumor tissues, thus rendering chemotherapy ineffective. To overcome this obstacle, two strategies – targeting transporter regulation and direct transporter inhibition – have been proposed. In this review, we focus on these strategies. We first introduce the latest findings on signaling pathways that could potentially be targeted to down-regulate P-gp and BCRP expression and/or transport activity. We then highlight in detail the new paradigm of P-gp and BCRP working as a “cooperative team of gatekeepers” at the blood-brain barrier, discuss its ramifications for brain cancer therapy, and summarize the latest findings on dual P-gp/BCRP inhibitors. Finally, we provide a brief summary with conclusions and outline the perspectives for future research endeavors in this field.
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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：
Fu LW
影响因子：
11.5
作者：
de Vries, Nienke A.;Zhao, Jin;van Tellingen, Olaf
通讯作者：
van Tellingen, Olaf
影响因子：
6.2
作者：
Agarwal S;Sane R;Oberoi R;Ohlfest JR;Elmquist WF
通讯作者：
Elmquist WF
影响因子：
4.7
作者：
Bihorel, Sebastien;Camenisch, Gian;Scherrmann, Jean-Michel
通讯作者：
Scherrmann, Jean-Michel
影响因子：
3.8
作者：
Cutler, Leanne;Howes, Colin;Jeffrey, Phil
通讯作者：
Jeffrey, Phil