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靶向精氨酸代谢途径治疗精氨酸依赖性癌症。

Targeting arginine metabolism pathway to treat arginine-dependent cancers.

作者信息

Qiu Fuming, Huang Jian, Sui Meihua

机构信息

Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Cancer Lett. 2015 Aug 1;364(1):1-7. doi: 10.1016/j.canlet.2015.04.020. Epub 2015 Apr 23.

Abstract

The significant disparities in metabolism between tumor and normal cells have inspired the development of metabolism-based anti-tumor therapeutics. Arginine is a semi-essential amino acid because normal cells can not only synthesize arginine de novo but also take up extracellular arginine. Several types of tumors have abnormalities in arginine metabolism enzymes and completely rely on extracellular arginine to support necessary biological processes. This property is referred to as arginine auxotrophy. Taking advantage of characteristic arginine auxotrophy in tumors, arginine deprivation, which is generally induced by the use of arginine deiminase (ADI) and arginase I, has been investigated as a novel strategy for cancer therapy. Arginine deprivation demonstrated promising efficacy against arginine-auxotrophic tumors. By integrating perspectives from both clinical oncologists and laboratory scientists, this article reviews the important aspects of arginine deprivation as a promising anticancer therapy.

摘要

肿瘤细胞与正常细胞之间显著的代谢差异激发了基于代谢的抗肿瘤疗法的发展。精氨酸是一种半必需氨基酸,因为正常细胞不仅可以从头合成精氨酸,还可以摄取细胞外的精氨酸。几种类型的肿瘤在精氨酸代谢酶方面存在异常,并且完全依赖细胞外精氨酸来支持必要的生物学过程。这种特性被称为精氨酸营养缺陷型。利用肿瘤中特有的精氨酸营养缺陷型,通过使用精氨酸脱亚氨酶(ADI)和精氨酸酶I来诱导精氨酸剥夺,已被作为一种新型癌症治疗策略进行研究。精氨酸剥夺对精氨酸营养缺陷型肿瘤显示出有前景的疗效。通过整合临床肿瘤学家和实验室科学家的观点,本文综述了精氨酸剥夺作为一种有前景的抗癌疗法的重要方面。

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