文章：

以铂为基础的癌症治疗的重新发现

The rediscovery of platinum-based cancer therapy

原文发布日期：2020-10-30

DOI: 10.1038/s41568-020-00308-y

类型: Review Article

开放获取: 否

英文摘要：

Platinum (Pt) compounds entered the clinic as anticancer agents when cisplatin was approved in 1978. More than 40 years later, even in the era of precision medicine and immunotherapy, Pt drugs remain among the most widely used anticancer drugs. As Pt drugs mainly target DNA, it is not surprising that recent insights into alterations of DNA repair mechanisms provide a useful explanation for their success. Many cancers have defective DNA repair, a feature that also sheds new light on the mechanisms of secondary drug resistance, such as the restoration of DNA repair pathways. In addition, genome-wide functional screening approaches have revealed interesting insights into Pt drug uptake. About half of cisplatin and carboplatin but not oxaliplatin may enter cells through the widely expressed volume-regulated anion channel (VRAC). The analysis of this heteromeric channel in tumour biopsies may therefore be a useful biomarker to stratify patients for initial Pt treatments. Moreover, Pt-based approaches may be improved in the future by the optimization of combinations with immunotherapy, management of side effects and use of nanodelivery devices. Hence, Pt drugs may still be part of the standard of care for several cancers in the coming years.

摘要翻译： 

铂(Pt)化合物于1978年顺铂获批时作为抗癌药物进入临床应用。四十余年后，即使在精准医疗和免疫治疗时代，铂类药物仍属最广泛使用的抗癌药物。由于铂类药物主要作用于DNA靶点，近期对DNA修复机制改变的研究成果能合理解释其成功应用也就不足为奇。许多癌症存在DNA修复缺陷，这一特征也为次级耐药机制（如DNA修复通路的重建）提供了新解读。此外，全基因组功能筛选研究对铂类药物摄取机制提出了创新见解：约半数顺铂与卡铂（奥沙利铂除外）可能通过广泛表达的容积调节性阴离子通道(VRAC)进入细胞。因此肿瘤活检组织中该异源多聚体通道的分析或可作为有用生物标志物，指导初始铂类治疗的患者分层。未来通过优化与免疫治疗的联用方案、加强不良反应管理、应用纳米递送装置等手段，铂类药物治疗策略有望进一步完善。由此可见，未来数年内铂类药物仍将是多种癌症的标准治疗方案组成部分。

原文链接：

The rediscovery of platinum-based cancer therapy