Choline kinase alpha-Putting the ChoK-hold on tumor metabolism

卷:63

Arlauckas, Sean P. ; Popov, Anatoliy V. ; Delikatny, E. James

Univ Penn

关键词: Choline kinase;    Lipid metabolism;    Tumor metabolism;    Inhibitors;   

DOI  :  10.1016/j.plipres.2016.03.005

学科分类：食品科学和技术

【 摘 要 】

It is well established that lipid metabolism is drastically altered during tumor development and response to therapy. Choline kinase alpha (ChoK alpha) is a key mediator of these changes, as it represents the first committed step in the Kennedy pathway of phosphatidylcholine biosynthesis and ChoK alpha expression is upregulated in many human cancers. ChoK alpha activity is associated with drug resistant, metastatic, and malignant phenotypes, and represents a robust biomarker and therapeutic target in cancer. Effective ChoK alpha inhibitors have been developed and have recently entered clinical trials. ChoK alpha's clinical relevance was, until recently, attributed solely to its production of second messenger intermediates of phospholipid synthesis. The recent discovery of a non-catalytic scaffolding function of ChoK alpha may link growth receptor signaling to lipid biogenesis and requires a reinterpretation of the design and validation of ChoK alpha inhibitors. Advances in positron emission tomography, magnetic resonance spectroscopy, and optical imaging methods now allow for a comprehensive understanding of ChoK alpha expression and activity in vivo. We will review the current understanding of ChoK alpha metabolism, its role in tumor biology and the development and validation of targeted therapies and companion diagnostics for this important regulatory enzyme. This comes at a critical time as ChoK alpha-targeting programs receive more clinical interest. (C) 2016 Elsevier Ltd. All rights reserved.