Cisplatin is a platinum-based drug, which remains among the most efficacious anticancer treatment options. Unfortunately, use of cisplatin is hindered by dose-limiting toxicities, including irreversible hearing loss, which can grossly affect patient quality of life. Cisplatin-induced ototoxicity is the result of cochlear hair cell damage through a mechanism that is poorly understood. However, cisplatin cytotoxicity is reliant on intracellular accumulation, a process that is largely dependent on the presence of particular membrane transporters. This review will provide an update on our current understanding of the various transporters known to be involved in the disposition and cytotoxicity of platinum drugs or their metabolites, as well as their role in mediating cisplatin-induced hearing loss. We also provide a summary of the successes and opportunities in therapeutically targeting membrane transporters to alleviate platinum-induced hearing loss. Moreover, we describe how this approach could be used to reduce the severity or onset of other adverse events associated with exposure to various forms of platinum drugs, without diminishing antitumor efficacy.

中文翻译：

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目前对膜转运蛋白作为顺铂引起的听力损失的调节剂或靶点的理解

顺铂是一种铂类药物，仍然是最有效的抗癌治疗选择之一。不幸的是，顺铂的使用受到剂量限制性毒性的阻碍，包括不可逆的听力损失，这会严重影响患者的生活质量。顺铂诱导的耳毒性是耳蜗毛细胞损伤的结果，其机制尚不清楚。然而，顺铂的细胞毒性依赖于细胞内积累，这一过程在很大程度上取决于特定膜转运蛋白的存在。这篇综述将更新我们目前对已知参与铂类药物或其代谢物的处置和细胞毒性的各种转运蛋白的理解，以及它们在介导顺铂引起的听力损失中的作用。我们还总结了治疗性靶向膜转运蛋白以减轻铂引起的听力损失的成功和机会。此外，我们描述了如何使用这种方法来降低与暴露于各种形式的铂类药物相关的其他不良事件的严重程度或发作，而不会降低抗肿瘤功效。