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肺癌中谷氨酰胺代谢的改变及治疗机会。

Altered glutamine metabolism and therapeutic opportunities for lung cancer.

机构信息

Department of Medicine, Emory University School of Medicine, Atlanta, GA.

Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA.

出版信息

Clin Lung Cancer. 2014 Jan;15(1):7-15. doi: 10.1016/j.cllc.2013.09.001. Epub 2013 Nov 13.

Abstract

Disordered cancer metabolism was described almost a century ago as an abnormal adaptation of cancer cells to glucose utilization especially in hypoxic conditions; the so-called Warburg effect. Greater research interest in this area in the past two decades has led to the recognition of the critical coupling of specific malignant phenotypes such as increased proliferation and resistance to programmed cell death (apoptosis) with altered metabolic handling of key molecules that are essential for normal cellular metabolism. The altered glucose metabolism frequently encountered in cancer cells has already been exploited for cancer diagnosis and treatment. The role of other glycolytic pathway intermediates and alternative pathways for energy generation and macromolecular synthesis in cancer cells has only become recognized more recently. Especially, the important role of altered glutamine metabolism in the malignant behavior of cancer cells and the potential exploitation of this cellular adaptation for therapeutic targeting has now emerged as an important area of cancer research. Expectedly, attempts to exploit this understanding for diagnostic and therapeutic ends are running apace with the elucidation of the complex metabolic alterations that accompany neoplastic transformation. Because lung cancer is a leading cause of cancer death with limited curative therapy options, careful elucidation of the mechanism and consequences of disordered cancer metabolism in lung cancer is warranted. This review provides a concise, systematic overview of the current understanding of the role of altered glutamine metabolism in cancer, and how these findings intersect with current and future approaches to lung cancer management.

摘要

近一个世纪前,人们就已经描述了癌症代谢紊乱,即癌细胞对葡萄糖的利用出现异常,尤其是在缺氧条件下,也就是所谓的“Warburg 效应”。在过去的二十年中,人们对这一领域的研究兴趣日益浓厚,这使得人们认识到特定恶性表型(如增殖增加和对程序性细胞死亡(细胞凋亡)的抵抗力)与关键分子的代谢处理之间存在关键联系,这些关键分子对正常细胞代谢至关重要。在癌细胞中经常遇到的改变的葡萄糖代谢已经被用于癌症的诊断和治疗。最近才认识到其他糖酵解途径中间产物和用于能量产生和大分子合成的替代途径在癌细胞中的作用。特别是,改变的谷氨酰胺代谢在癌细胞恶性行为中的重要作用,以及对这种细胞适应性进行治疗靶向的潜力,现在已成为癌症研究的一个重要领域。可以预期,随着阐明伴随肿瘤转化的复杂代谢改变,人们将尝试利用这一认识来进行诊断和治疗。由于肺癌是癌症死亡的主要原因,且治疗选择有限,因此需要仔细阐明肺癌中紊乱的癌症代谢的机制和后果。这篇综述提供了对改变的谷氨酰胺代谢在癌症中的作用的当前理解的简要、系统的概述,以及这些发现如何与当前和未来的肺癌管理方法相交织。

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