Marques Andrezza Viviany Lourenço, Ruginsk Bruna Estelita, Prado Larissa de Oliveira, de Lima Diogo Eugênio, Daniel Isabelle Watanabe, Moure Vivian Rotuno, Valdameri Glaucio
Graduate Program in Pharmaceutical Sciences, Laboratory of Cancer Drug Resistance, Federal University of Parana, Curitiba, Paraná, Brazil.
Graduate Program in Pharmaceutical Sciences, Laboratory of Cancer Drug Resistance, Federal University of Parana, Curitiba, Paraná, Brazil.
Biochim Biophys Acta Mol Cell Res. 2025 Feb;1872(2):119878. doi: 10.1016/j.bbamcr.2024.119878. Epub 2024 Nov 20.
Multidrug resistance (MDR) poses one of the primary challenges for cancer treatment, especially in cases of metastatic disease. Various mechanisms contribute to MDR, including the overexpression of ATP-binding cassette (ABC) proteins. In this context, we reviewed the literature to establish a correlation between the overexpression of ABC proteins and MDR in cancer, considering both in vitro and clinical studies. Initially, we presented an overview of the seven subfamilies of ABC proteins, along with the subcellular localization of each protein. Subsequently, we identified a panel of 20 ABC proteins (ABCA1-3, ABCA7, ABCB1-2, ABCB4-6, ABCC1-5, ABCC10-11, ABCE1, ABCF2, ABCG1, and ABCG2) associated with MDR. We also emphasize the significance of drug sequestration by certain ABC proteins into intracellular compartments. Among the anticancer drugs linked to MDR, 29 were definitively identified as substrates for at least one of the three most crucial ABC transporters: ABCB1, ABCC1, and ABCG2. We further discussed that the most commonly used drugs in standard regimens for mainly breast cancer, lung cancer, and acute lymphoblastic leukemia could be subject to MDR mediated by ABC transporters. Collectively, these insights will aid in conducting new studies aimed at a deeper understanding of the clinical MDR mediated by ABC proteins and in designing more effective pharmacological treatments to enhance the objective response rate in cancer patients.
多药耐药（MDR）是癌症治疗面临的主要挑战之一，尤其是在转移性疾病的情况下。多种机制导致MDR，包括ATP结合盒（ABC）蛋白的过表达。在此背景下，我们回顾了文献，以确定ABC蛋白过表达与癌症MDR之间的相关性，同时考虑了体外研究和临床研究。首先，我们概述了ABC蛋白的七个亚家族，以及每种蛋白的亚细胞定位。随后，我们确定了一组与MDR相关的20种ABC蛋白（ABCA1 - 3、ABCA7、ABCB1 - 2、ABCB4 - 6、ABCC1 - 5、ABCC10 - 11、ABCE1、ABCF2、ABCG1和ABCG2）。我们还强调了某些ABC蛋白将药物隔离到细胞内区室的重要性。在与MDR相关的抗癌药物中，有29种被明确确定为三种最关键的ABC转运蛋白（ABCB1、ABCC1和ABCG2）中至少一种的底物。我们进一步讨论了主要用于乳腺癌、肺癌和急性淋巴细胞白血病的标准方案中最常用的药物可能会受到ABC转运蛋白介导的MDR的影响。总的来说，这些见解将有助于开展新的研究，旨在更深入地了解由ABC蛋白介导的临床MDR，并设计更有效的药物治疗方案，以提高癌症患者的客观缓解率。
