Wind N S, Holen I
Academic Unit of Clinical Oncology, DU10, Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK.
Int J Breast Cancer. 2011;2011:967419. doi: 10.4061/2011/967419. Epub 2011 Feb 24.
The development of multidrug resistance (MDR) and subsequent relapse on therapy is a widespread problem in breast cancer, but our understanding of the underlying molecular mechanisms is incomplete. Numerous studies have aimed to establish the role of drug transporter pumps in MDR and to link their expression to response to chemotherapy. The ATP-binding cassette (ABC) transporters are central to breast cancer MDR, and increases in ABC expression levels have been shown to correlate with decreases in response to various chemotherapy drugs and a reduction in overall survival. But as there is a large degree of redundancy between different ABC transporters, this correlation has not been seen in all studies. This paper provides an introduction to the key molecules associated with breast cancer MDR and summarises evidence of their potential roles reported from model systems and clinical studies. We provide possible explanations for why despite several decades of research, the precise role of ABC transporters in breast cancer MDR remains elusive.
多药耐药(MDR)的发展以及随后治疗中的复发是乳腺癌中普遍存在的问题,但我们对其潜在分子机制的理解并不完整。众多研究旨在确定药物转运泵在多药耐药中的作用,并将它们的表达与化疗反应联系起来。ATP结合盒(ABC)转运蛋白是乳腺癌多药耐药的核心,ABC表达水平的增加已被证明与对各种化疗药物反应的降低以及总生存期的缩短相关。但由于不同ABC转运蛋白之间存在很大程度的冗余,这种相关性在所有研究中并非都能看到。本文介绍了与乳腺癌多药耐药相关的关键分子,并总结了模型系统和临床研究中报道的它们潜在作用的证据。我们对尽管经过几十年研究,ABC转运蛋白在乳腺癌多药耐药中的确切作用仍不清楚的原因提供了可能的解释。