New trends for overcoming ABCG2/BCRP-mediated resistance to cancer therapies.
New trends for overcoming ABCG2/BCRP-mediated resistance to cancer therapies.
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DOI：
10.1186/s13046-015-0275-x
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发表时间：
2015-12-30
期刊：
影响因子：
--
通讯作者：
Li F
中科院分区：
文献类型：
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作者：
Westover D;Li F
ATP结合盒（ABC）转运蛋白是一个跨膜蛋白超家族，在耐药性的形成中起着关键作用。这种现象在肿瘤学中尤其重要，已知超家族成员ABCG 2（也称为BCRP -乳腺癌耐药蛋白）与数十种作为ABCG 2底物的抗癌剂相互作用。除了作为ABCG 2转运蛋白底物的细胞毒性和靶向药物的经过充分研究和充分审查的列表之外，越来越多的工作将ABCG 2与多种光动力治疗（PDT）药物联系起来，并且有有限的证据表明ABCG 2也可能在抵抗放射治疗中发挥作用。此外，在过去几年中，ABC转运蛋白研究在治疗开发方面的重点已经开始转移。这种转变已经从使用泵抑制剂逆转耐药性，转向开发这些外排泵蛋白质的不良底物的治疗剂。这种方法可能导致开发完全规避ABC转运蛋白介导的耐药性的药物方案。在这里，我们的目的是审查：1）最近的发现，进一步表征了ABCG 2在肿瘤学中的作用，2）逆转和规避ABC转运蛋白介导的抗癌治疗耐药性的进展。
ATP-binding cassette (ABC) transporters make up a superfamily of transmembrane proteins that play a critical role in the development of drug resistance. This phenomenon is especially important in oncology, where superfamily member ABCG2 (also called BCRP – breast cancer resistance protein) is known to interact with dozens of anti-cancer agents that are ABCG2 substrates. In addition to the well-studied and well-reviewed list of cytotoxic and targeted agents that are substrates for the ABCG2 transporter, a growing body of work links ABCG2 to multiple photodynamic therapy (PDT) agents, and there is a limited body of evidence suggesting that ABCG2 may also play a role in resistance to radiation therapy. In addition, the focus of ABC transporter research in regards to therapeutic development has begun to shift in the past few years. The shift has been away from using pump inhibitors for reversing resistance, toward the development of therapeutic agents that are poor substrates for these efflux pump proteins. This approach may result in the development of drug regimens that circumvent ABC transporter-mediated resistance entirely. Here, it is our intention to review: 1) recent discoveries that further characterize the role of ABCG2 in oncology, and 2) advances in reversing and circumventing ABC transporter-mediated resistance to anti-cancer therapies.