Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems , Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190 , P.R. China.
University of Chinese Academy of Sciences , Beijing 100049 , P.R. China.
Chem Res Toxicol. 2019 Aug 19;32(8):1469-1486. doi: 10.1021/acs.chemrestox.9b00204. Epub 2019 Aug 5.
Cisplatin is one of the most widely used chemotherapeutic agents for various solid tumors in the clinic due to its high efficacy and broad spectrum. The antineoplastic activity of cisplatin is mainly due to its ability to cross-link with DNA, thus blocking transcription and replication. Unfortunately, the clinical use of cisplatin is limited by its severe, dose-dependent toxic side effects. There are approximately 40 specific toxicities of cisplatin, among which nephrotoxicity is the most common one. Other common side effects include ototoxicity, neurotoxicity, gastrointestinal toxicity, hematological toxicity, cardiotoxicity, and hepatotoxicity. These side effects together reduce the life quality of patients and require lowering the dosage of the drug, even stopping administration, thus weakening the treatment effect. Few effective measures exist clinically against these side effects because the exact mechanisms of various side effects from cisplatin remain still unclear. Therefore, substantial effort has been made to explore the complicated biochemical processes involved in the toxicology of cisplatin, aiming to identify effective ways to reduce or eradicate its toxicity. This review summarizes and reviews the updated advances in the toxicological research of cisplatin. We anticipate to provide insights into the understanding of the mechanisms underlying the side effects of cisplatin and designing comprehensive therapeutic strategies involving cisplatin.
顺铂是临床上治疗各种实体瘤最广泛使用的化疗药物之一,因为它具有高效广谱的特点。顺铂的抗肿瘤活性主要归因于其与 DNA 交联的能力,从而阻断转录和复制。不幸的是,顺铂的临床应用受到其严重的、剂量依赖性毒性副作用的限制。顺铂有大约 40 种特异性毒性,其中肾毒性是最常见的一种。其他常见的副作用包括耳毒性、神经毒性、胃肠道毒性、血液毒性、心脏毒性和肝毒性。这些副作用一起降低了患者的生活质量,需要降低药物剂量,甚至停止给药,从而削弱了治疗效果。由于顺铂引起的各种副作用的确切机制仍不清楚,临床上几乎没有有效的措施来对抗这些副作用。因此,人们已经做出了巨大的努力来探索顺铂毒理学中涉及的复杂生化过程,旨在寻找有效减少或消除其毒性的方法。这篇综述总结和回顾了顺铂毒理学研究的最新进展。我们希望为理解顺铂副作用的机制以及设计涉及顺铂的综合治疗策略提供一些见解。