Multidrug resistance is a key determinant of cancer chemotherapy failure. One of the major causes of multidrug resistance is the enhanced efflux of drugs by membrane ABC transporters. Targeting ABC transporters projects a promising approach to eliminating or suppressing drug resistance in cancer treatment. To reveal the functional mechanisms of ABC transporters in drug resistance, extensive studies have been conducted from identifying drug binding sites to elucidating structural dynamics. In this review article, we examined the recent crystal structures of ABC proteins to depict the functionally important structural elements, such as domains, conserved motifs, and critical amino acids that are involved in ATP-binding and drug efflux. We inspected the drug-binding sites on ABC proteins and the molecular mechanisms of various substrate interactions with the drug binding pocket. While our continuous battle against drug resistance is far from over, new approaches and technologies have emerged to push forward our frontier. Most recent developments in anti-MDR strategies include P-gp inhibitors, RNA-interference, nano-medicines, and delivering combination strategies. With the advent of the ‘Omics’ era – genomics, epigenomics, transcriptomics, proteomics, and metabolomics – these disciplines play an important role in fighting the battle against chemoresistance by further unraveling the molecular mechanisms of drug resistance and shed light on medical therapies that specifically target MDR.

多药耐药性是癌症化疗失败的关键决定因素。多重耐药性的主要原因之一是膜ABC转运蛋白增强了药物的外排。靶向ABC转运蛋白为消除或抑制癌症治疗中的耐药性提供了一种有前途的方法。为了揭示ABC转运蛋白在耐药性中的功能机制，已经进行了广泛的研究，从鉴定药物结合位点到阐明结构动力学。在这篇综述文章中，我们检查了ABC蛋白的最新晶体结构，以描述功能上重要的结构元素，例如与ATP结合和药物外排有关的结构域，保守基序和关键氨基酸。我们检查了ABC蛋白上的药物结合位点以及与药物结合袋的各种底物相互作用的分子机制。尽管我们与抗药性的持续斗争还没有结束，但已经出现了新的方法和技术来推动我们的前沿。抗MDR策略的最新进展包括P-gp抑制剂，RNA干扰，纳米药物和联合给药策略。随着“组学”时代的到来–基因组学，表观基因组学，转录组学，蛋白质组学和代谢组学–这些学科通过进一步阐明耐药性的分子机制并阐明专门针对医学疗法的分子机制，在与化学抗性的斗争中发挥了重要作用。目标MDR。尽管我们与抗药性的持续斗争还没有结束，但已经出现了新的方法和技术来推动我们的前沿。抗MDR策略的最新进展包括P-gp抑制剂，RNA干扰，纳米药物和联合给药策略。随着“组学”时代的到来–基因组学，表观基因组学，转录组学，蛋白质组学和代谢组学–这些学科通过进一步阐明耐药性的分子机制并阐明专门针对医学疗法的分子机制，在与化学抗性的斗争中发挥了重要作用。目标MDR。尽管我们与抗药性的持续斗争还没有结束，但已经出现了新的方法和技术来推动我们的前沿。抗MDR策略的最新进展包括P-gp抑制剂，RNA干扰，纳米药物和联合给药策略。随着“组学”时代的到来–基因组学，表观基因组学，转录组学，蛋白质组学和代谢组学–这些学科通过进一步阐明耐药性的分子机制并阐明专门针对医学疗法的分子机制，在与化学抗性的斗争中发挥了重要作用。目标MDR。