Department of Medical Oncology, Erasmus Medical Center Rotterdam-Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Drug Resist Updat. 2011 Feb;14(1):22-34. doi: 10.1016/j.drup.2010.12.002. Epub 2011 Jan 20.
Platinum-based drugs are among the most active anticancer agents and are successfully used in a wide variety of human malignancies. However, acquired and/or intrinsic resistance still represent a major limitation. Lately, in particular mechanisms leading to impaired uptake and/or decreased cellular accumulation of platinum compounds have attracted attention. In this review, we focus on the role of active platinum uptake and efflux systems as determinants of platinum sensitivity and -resistance and their contribution to platinum pharmacokinetics (PK) and pharmacodynamics (PD). First, the three mostly used platinum-based anticancer agents as well as the most promising novel platinum compounds in development are put into clinical perspective. Next, we describe the presently known potential platinum transporters--with special emphasis on organic cation transporters (OCTs)--and discuss their role on clinical outcome (i.e. efficacy and adverse events) of platinum-based chemotherapy. In addition, transporter-mediated tumour resistance, the impact of potential platinum transporter-mediated drug-drug interactions, and the role of drug transporters in the renal elimination of platinum compounds are discussed.
铂类药物是最有效的抗癌药物之一，已成功应用于多种人类恶性肿瘤。然而，获得性和/或内在耐药性仍然是一个主要的限制。最近，特别是导致铂化合物摄取和细胞内积累减少的机制引起了人们的关注。在这篇综述中，我们重点关注主动铂摄取和外排系统作为铂敏感性和耐药性决定因素的作用，以及它们对铂药代动力学（PK）和药效学（PD）的贡献。首先，我们将目前临床使用的三种最常用的铂类抗癌药物和最有前途的新型铂类化合物进行了临床观察。接下来，我们描述了目前已知的潜在铂转运体——特别强调有机阳离子转运体（OCTs）——并讨论了它们在铂类化疗的临床结果（即疗效和不良反应）中的作用。此外，还讨论了转运体介导的肿瘤耐药性、潜在的铂转运体介导的药物-药物相互作用的影响，以及药物转运体在铂类化合物肾排泄中的作用。
