Bugde Piyush, Biswas Riya, Merien Fabrice, Lu Jun, Liu Dong-Xu, Chen Mingwei, Zhou Shufeng, Li Yan
a School of Science , Auckland University of Technology , Auckland , New Zealand.
b School of Science, AUT Roche Diagnostic Laboratory , Auckland University of Technology , Auckland , New Zealand.
Expert Opin Ther Targets. 2017 May;21(5):511-530. doi: 10.1080/14728222.2017.1310841. Epub 2017 Apr 3.
Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect. Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters. We integrated our current knowledge at different levels from molecular biology to clinical trials. We also discussed potential therapeutic strategies of targeting ABC transporters to reverse MDR in cancer cells. Expert opinion: Involvement of various ABC transporters to cancer MDR lays the foundation for developing tailored therapies that can overcome MDR. An ideal MDR reversal agent should have broad-spectrum ABC-transporter inhibitory activity, be potent, have good pharmacokinetics, have no trans-stimulation effects, and have low or no toxicity. Alternatively, nanotechnology-based drug delivery systems containing both the cytotoxic drug and reversing agent may represent a useful approach to reversing MDR with minimal off-target toxicity.
尽管有多种传统和新型治疗方法，包括手术、化疗、放疗、免疫疗法和生物靶向治疗，但大多数播散性癌症仍然致命。化疗治疗癌症失败的一个主要因素是多药耐药性（MDR）的产生。癌细胞中各种ABC转运蛋白的过表达可以有效地将抗癌药物从细胞中清除，从而使药物失去作用。涵盖领域：在本综述中，我们总结了与ABC转运蛋白的机制、功能和调控相关的正在进行的研究。我们整合了从分子生物学到临床试验不同层面的现有知识。我们还讨论了靶向ABC转运蛋白以逆转癌细胞中MDR的潜在治疗策略。专家观点：各种ABC转运蛋白参与癌症MDR为开发能够克服MDR的定制疗法奠定了基础。理想的MDR逆转剂应具有广谱ABC转运蛋白抑制活性、效力强、药代动力学良好、无转刺激作用且毒性低或无毒性。或者，包含细胞毒性药物和逆转剂的基于纳米技术的药物递送系统可能是一种以最小的脱靶毒性逆转MDR的有用方法。
