Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Curr Drug Metab. 2011 Oct;12(8):793-807. doi: 10.2174/138920011798357060.
The effectiveness of many anticancer agents is dependent on their disposition to the intracellular space of cancerous tissue. Accumulation of anticancer drugs at their sites of action can be altered by both uptake and efflux transport proteins, however the majority of research on the disposition of anticancer drugs has focused on drug efflux transporters and their ability to confer multidrug resistance. Here we review the roles of uptake transporters of the SLC22A and SLCO families in the context of cancer therapy. The many first-line anticancer drugs that are substrates of organic cation transporters (OCTs) organic cation/carnitine transporters (OCTNs) and organic anion- transporting polypeptides (OATPs) are summarized. In addition, where data is available a comparison of the localization of drug uptake transporters in healthy and cancerous tissues is provided. Expression of drug uptake transporters increases the sensitivity of cancer cell lines to anticancer substrates. Furthermore, early observational studies have suggested a causal link between drug uptake transporter expression and positive outcome in some cancers. Quantification of drug transporters by mass spectrometry will provide an essential technique for generation of expression data during future observational clinical studies. Screening of drug uptake transporter expression in primary tumors may help differentiate between susceptible and resistant cancers prior to therapy.
许多抗癌药物的疗效取决于它们在癌组织细胞内空间的分布。抗癌药物在其作用部位的积累可以通过摄取和外排转运蛋白来改变，然而，大多数关于抗癌药物分布的研究都集中在药物外排转运蛋白及其赋予多药耐药性的能力上。在这里，我们回顾了 SLC22A 和 SLCO 家族的摄取转运蛋白在癌症治疗中的作用。总结了许多一线抗癌药物是有机阳离子转运体（OCTs）、有机阳离子/肉碱转运体（OCTNs）和有机阴离子转运多肽（OATPs）的底物。此外，在有数据的情况下，还提供了药物摄取转运体在健康组织和癌组织中的定位比较。药物摄取转运体的表达增加了癌细胞系对抗癌底物的敏感性。此外，早期观察性研究表明，在某些癌症中，药物摄取转运体的表达与阳性结果之间存在因果关系。通过质谱定量药物转运体将为未来观察性临床研究中的表达数据生成提供一项重要技术。在治疗前对原发性肿瘤中药物摄取转运体的表达进行筛选，可能有助于区分敏感和耐药性癌症。
