Grupo de Investigación en Macromoléculas, Departamento de Química, Universidad Nacional de Colombia-Sede Bogotá, 5997, Bogotá, Colombia.
Institute of Organic Chemistry, University of Regensburg, 93040 Regensburg, Germany.
Med Res Rev. 2017 Sep;37(5):987-1050. doi: 10.1002/med.21428. Epub 2016 Dec 22.
Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2). The first two transporters have been widely studied already and reviews summarized the results. The ABCG2 protein has been a subject of intense study since its discovery as its overexpression has been detected in resistant cell lines in numerous types of human cancers. To date, a long list of modulators of ABCG2 exists and continues to increase. However, little is known about the clinical consequences of ABCG2 modulation. This makes the design of novel, potent, and nontoxic inhibitors of this efflux protein a major challenge to reverse MDR and thereby increase the success of chemotherapy. The aim of the present review is to describe and highlight specific and nonspecific modulators of ABCG2 reported to date based on the selectivity of the compounds, as many of them are effective against one or more ABC transport proteins.
癌细胞的多药耐药性（MDR）是对多种结构和功能上无关的抗癌药物产生耐药性的现象。这种现象已成为癌症化疗的主要障碍，严重影响了临床疗效。MDR 与细胞内药物外排的增加有关，这种外排是由涉及 ATP 结合盒（ABC）转运蛋白的能量依赖机制介导的，主要是 P 糖蛋白（ABCB1）、多药耐药相关蛋白-1（ABCC1）和乳腺癌耐药蛋白（ABCG2）。前两种转运蛋白已经得到了广泛的研究，综述总结了这些研究的结果。自从发现 ABCG2 蛋白以来，由于其在许多类型的人类癌症的耐药细胞系中过表达，该蛋白一直是研究的热点。迄今为止，已经有一长串 ABCG2 的调节剂存在，并在不断增加。然而，对于 ABCG2 调节的临床后果知之甚少。这使得设计新型、有效且无毒的这种外排蛋白抑制剂成为逆转 MDR 从而提高化疗成功率的主要挑战。本综述的目的是描述和强调迄今为止报道的 ABCG2 的特异性和非特异性调节剂，因为其中许多化合物对一种或多种 ABC 转运蛋白有效。
