Department of Biochemical Sciences, Charles University, Hradec Králové, Czech Republic, European Union.
Drug Metab Rev. 2011 Nov;43(4):540-57. doi: 10.3109/03602532.2011.609174. Epub 2011 Sep 26.
Anthracycline antibiotic doxorubicin (DOX) belongs among the most important antineoplastics used in cancer therapy. Unfortunately, its cytostatic effect in therapeutic doses is frequently insufficient; but the use of higher DOX doses is limited by the development of systemic toxicity, especially cardiotoxicity. Therefore, a searching for some possibilities of how to increase DOX efficacy in cancer cells, and minimizing associated toxicities to noncancerous tissues, is in the forefront of scientific research. Many approaches are based on altered DOX metabolism. The classical strategies include an enhancing of DOX uptake by cancer cells and/or an activation of DOX prodrug within cancer cells via liposomal encapsulation or conjugation with antibodies, peptides, or synthetic polymers. The diminishing of DOX deactivation, restriction of DOX efflux from cancer cells, decreased antioxidant defense of cancer cells, changes in cell cycle, or modulation of signaling pathways represent newer approaches in increasing DOX toxicity in tumors. Each way has certain advantages and limitations. The aim of this review was not to collect all reported results, but to bring an overview of various approaches and a summary of their principles. Possible advantages, disadvantages, and further perspectives are discussed and evaluated.
蒽环类抗生素阿霉素（DOX）属于癌症治疗中最重要的抗肿瘤药物之一。不幸的是，其在治疗剂量下的细胞抑制作用常常不足；但由于全身毒性的发展，特别是心脏毒性，高剂量 DOX 的使用受到限制。因此，寻找一些方法来提高 DOX 在癌细胞中的疗效，同时将相关毒性最小化到非癌组织，是科学研究的前沿。许多方法都基于改变 DOX 的代谢。经典策略包括通过脂质体包封或与抗体、肽或合成聚合物缀合来增强癌细胞对 DOX 的摄取和/或激活癌细胞内的 DOX 前药。减少 DOX 的失活、限制 DOX 从癌细胞中的流出、降低癌细胞的抗氧化防御、改变细胞周期或调节信号通路是增加 DOX 在肿瘤中的毒性的新方法。每种方法都有一定的优点和局限性。本文的目的不是收集所有报道的结果，而是提供各种方法的概述及其原理的总结。讨论和评估了可能的优点、缺点和进一步的前景。
