Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133 Milan, Italy.
Curr Med Chem. 2011;18(27):4237-49. doi: 10.2174/092986711797189682.
ATP-binding cassette (ABC) transporters are a large family of proteins implicated in physiological cellular functions. Selected components of the family play a well-recognized role in extruding conventional cytotoxic antitumor agents and molecularly targeted drugs from cells. Some lines of evidence also suggest links between transporters and tumor cell survival, in part unrelated to efflux. However, the study of the precise mechanisms regulating the function of drug transporters (e.g., posttranslational modifications such as glycosylation) is still in its infancy. A better definition of the molecular events clarifying the regulation of transporter levels including regulation by microRNAs may contribute to provide new molecular tools to target such a family of transporters. The present review focuses on the biological aspects that implicate ABC transporters in resistance of tumor cells, including cancer stem cells. Molecular analysis of well-known preclinical systems as well as of cancer stem cell models supports the notion that ABC transporters represent amenable targets for modulation of the efficacy of antitumor agents endowed with different molecular features. Recent achievements regarding tumor cell biology are expected to provide a rationale for developing novel inhibitors that target ABC transporters implicated in drug resistance.
三磷酸腺苷结合盒（ABC）转运蛋白是一个庞大的蛋白质家族，涉及多种生理细胞功能。该家族的某些成分在将传统细胞毒性抗肿瘤药物和分子靶向药物从细胞中排出方面发挥着公认的作用。一些证据还表明，转运蛋白与肿瘤细胞存活之间存在联系，部分与外排无关。然而，关于调节药物转运蛋白功能的精确机制（例如，翻译后修饰，如糖基化）的研究仍处于起步阶段。更明确地阐明转运蛋白水平的调节（包括 microRNA 的调节）的分子事件的定义可能有助于提供新的分子工具来靶向这种转运蛋白家族。本综述重点介绍了 ABC 转运蛋白在肿瘤细胞耐药性（包括癌症干细胞）中的生物学方面。对知名临床前系统和癌症干细胞模型的分子分析支持了这样一种观点，即 ABC 转运蛋白是调节具有不同分子特征的抗肿瘤药物疗效的可行靶点。关于肿瘤细胞生物学的最新研究成果有望为开发靶向耐药性相关 ABC 转运蛋白的新型抑制剂提供理论依据。
