Department of Biochemistry, AIIMS, Jodhpur, India.
Indian Institute of Technology (IIT) Madras, Chennai, India.
J Drug Target. 2022 Nov;30(9):927-947. doi: 10.1080/1061186X.2022.2091578. Epub 2022 Jun 26.
ATP-binding cassette (ABC) transporters are membrane-spanning proteins involved in cholesterol homeostasis, transport of various molecules in and out of cells and organelles, oxidative stress, immune recognition, and drug efflux. They are long implicated in the development of multidrug resistance in cancer chemotherapy. Existing clinical and molecular evidence has also linked ABC transporters with cancer pathogenesis, prognostics, and therapy. In this review, we aim to provide a comprehensive update on all ABC transporters and their roles in drug resistance in breast cancer (BC). For solid tumours such as BC, various ABC transporters are highly expressed in less differentiated subtypes and metastases. ABCA1, ABCB1 and ABCG2 are key players in BC chemoresistance. Restraining these transporters has evolved as a possible mechanism to reverse this phenomenon. Further, ABCB1 and ABCC1 are important in BC prognosis. Newer therapeutic approaches have been developed to target all these molecules to dysregulate their effect, reduce cell viability, induce apoptosis, and increase drug sensitivity. In the future, targeted therapy for specific genetic variations and upstream or downstream molecules can help improve patient prognosis.
三磷酸腺苷结合盒(ABC)转运蛋白是一种跨膜蛋白,参与胆固醇稳态、细胞和细胞器内外各种分子的转运、氧化应激、免疫识别和药物外排。它们长期以来与癌症化疗中的多药耐药性的发展有关。现有的临床和分子证据也将 ABC 转运蛋白与癌症的发病机制、预后和治疗联系起来。在这篇综述中,我们旨在全面更新所有 ABC 转运蛋白及其在乳腺癌(BC)耐药性中的作用。对于 BC 等实体肿瘤,各种 ABC 转运蛋白在分化程度较低的亚型和转移中高度表达。ABCA1、ABCB1 和 ABCG2 是 BC 化疗耐药性的关键因素。抑制这些转运蛋白已成为逆转这种现象的一种可能机制。此外,ABCB1 和 ABCC1 在 BC 预后中很重要。已经开发出了新的治疗方法来靶向所有这些分子,以使其作用失调,降低细胞活力,诱导细胞凋亡,并增加药物敏感性。在未来,针对特定遗传变异和上下游分子的靶向治疗可以帮助改善患者的预后。