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摘要
铂类抗癌药物包括顺铂、卡铂和奥沙利铂,是临床上用于治疗多种癌症的一类重要药物。这些药物的毒性作用是通过链间形成和链内交联,或者细胞核DNA上的铂加合物而介导的。也有证据表明线粒体DNA在背根神经节神经元中对铂加合物损伤很敏感。尽管所有的铂类药物都具有相似的DNA加合物,但它们在活化、系统毒性和耐受性方面却截然不同。众所周知,铂类药物有较为严重的神经毒性和胃肠道副作用,这是导致剂量限制和治疗中止影响抗癌治疗效果的主要原因。 在非神经细胞中较多的证据表明,铜转运系统与铂类药物的敏感性和耐药性有关。关于铜转运蛋白在中枢和外周神经系统中的作用的研究最少。目前尚不清楚神经元是否对铂类药物更敏感,药物清除不足,或铂积累是否影响细胞内铜状态和铜介导的功能。了解这些机制很重要,因为神经毒性是铂类药物治疗过程中的主要副作用。 本文综述了铜转运在药物流入中的作用,以铂类为基础的药物引起的药物激活和副作用的差异,以及与中枢和外周神经病变和胃肠道毒性的关系。
关键词: 神经毒性,顺铂,卡铂,奥沙利铂,铜转运蛋白,转铜伴侣。
Current Medicinal Chemistry
Title:Neurotoxicity Associated with Platinum-Based Anti-Cancer Agents: What are the Implications of Copper Transporters?
Volume: 24 Issue: 15
关键词: 神经毒性,顺铂,卡铂,奥沙利铂,铜转运蛋白,转铜伴侣。
摘要: Platinum-based anti-cancer agents, which include cisplatin, carboplatin and oxaliplatin, are an important class of drugs used in clinical setting to treat a variety of cancers. The cytotoxic efficacy of these drugs is mediated by the formation of inter-strand and intrastrand crosslinks, or platinum adducts on nuclear DNA. There is also evidence demonstrating that mitochondrial DNA is susceptible to platinum-adduct damage in dorsal root ganglia neurons. Although all platinum-based agents form similar DNA adducts, they are quite different in terms of activation, systemic toxicity and tolerance. Platinum-based agents are well known for their neurotoxicity and gastrointestinal side-effects which are major causes for dose limitation and treatment discontinuation compromising the efficacy of anti-cancer treatment.
Accumulating evidence in non-neuronal cells shows that the copper transport system is associated with platinum drug sensitivity and resistance. There is minimal research concerning the role of copper transporters within the central and peripheral nervous systems. It is unclear whether neurons are more sensitive to platinum-based drugs, are insufficient in drug clearance, or whether platinum accumulation affects intracellular copper status and coppermediated functions. Understanding these mechanisms is important as neurotoxicity is the predominant side-effect of platinum-based chemotherapy. This review highlights the role of copper transpor ters in drug influx, differences in drug activation and side-effects caused by platinum-based agents, as well as their association with central and peripheral neuropathies and gastrointestinal toxicities.Export Options
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Cite this article as:
Neurotoxicity Associated with Platinum-Based Anti-Cancer Agents: What are the Implications of Copper Transporters?, Current Medicinal Chemistry 2017; 24 (15) . https://dx.doi.org/10.2174/0929867324666170112095428
DOI https://dx.doi.org/10.2174/0929867324666170112095428 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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