Liu Hao, Wang Haiyan, Xiang Dingcheng, Guo Wangang
Department of Cardiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'An 710038, China.
Mini Rev Med Chem. 2017;17(1):44-50. doi: 10.2174/1389557516666160621083659.
The anthracycline doxorubicin (DOX) has proved to be one of the most widely used and most effective antitumor drugs since its emergence in the 1960s. However, the utility of DOX is compromised by its potential lethal cardiotoxicity. In this review we summarize development in prevention and management of DOX-induced cardiotoxicity comprehensively.
Strategies to enhance DOX efficacy in cancer cells while minimizing associated cardiotoxicity may prove clinically valuable. Employment of DOX derivatives, including currently available mitoxantrone and epirubicin, has been testified in several clinical trials. Several cardioprotective agents, including dexrazoxane, statins, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, and etc., have been developed and tested in animal and clinical trials.
Several strategies have been reported on the prevention and management of DOX-elicited cardiotoxicity, and many of them await verification from large scale clinical trials. Dexrazoxane has been approved to prevent and treat side effects of DOX, although concerns still exist that it might increase incidence of some kind of malignant tumors. Promising findings in autophagy, RNA binding protein quaking and statins encourage further research developing strategies by which heart protection and cancer cell killing are achieved simutaneously.
自20世纪60年代出现以来,蒽环类药物阿霉素(DOX)已被证明是应用最广泛、最有效的抗肿瘤药物之一。然而,DOX的效用因其潜在的致命心脏毒性而受到影响。在本综述中,我们全面总结了DOX诱导的心脏毒性的预防和管理方面的进展。
在提高DOX对癌细胞的疗效同时将相关心脏毒性降至最低的策略可能具有临床价值。DOX衍生物的应用,包括目前可用的米托蒽醌和表柔比星,已在多项临床试验中得到验证。几种心脏保护剂,包括右丙亚胺、他汀类药物、血管紧张素转换酶抑制剂、钙通道阻滞剂、β受体阻滞剂等,已在动物和临床试验中开发和测试。
已有多种预防和管理DOX引起的心脏毒性的策略报道,其中许多策略有待大规模临床试验验证。右丙亚胺已被批准用于预防和治疗DOX的副作用,尽管人们仍然担心它可能会增加某些恶性肿瘤的发病率。自噬、RNA结合蛋白震颤和他汀类药物方面的有前景的研究结果鼓励进一步开展研究,以开发同时实现心脏保护和癌细胞杀伤的策略。