title: Choline kinase alpha-Putting the ChoK-hold on tumor metabolism.
abstract: It is well established that lipid metabolism is drastically altered during tumor development and response to therapy. Choline kinase alpha (ChoKα) is a key mediator of these changes, as it represents the first committed step in the Kennedy pathway of phosphatidylcholine biosynthesis and ChoKα expression is upregulated in many human cancers. ChoKα activity is associated with drug resistant, metastatic, and malignant phenotypes, and represents a robust biomarker and therapeutic target in cancer. Effective ChoKα inhibitors have been developed and have recently entered clinical trials. ChoKα'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 ChoKα may link growth receptor signaling to lipid biogenesis and requires a reinterpretation of the design and validation of ChoKα inhibitors. Advances in positron emission tomography, magnetic resonance spectroscopy, and optical imaging methods now allow for a comprehensive understanding of ChoKα expression and activity in vivo. We will review the current understanding of ChoKα 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 ChoKα-targeting programs receive more clinical interest.
authors.affiliation: Department of Radiology, 317 Anatomy-Chemistry Building, 3620 Hamilton Walk, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Arlauckas
authors.affiliation: Department of Radiology, 317 Anatomy-Chemistry Building, 3620 Hamilton Walk, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Anatoliy V
authors.initials: AV
authors.lastname: Popov
authors.affiliation: Department of Radiology, 317 Anatomy-Chemistry Building, 3620 Hamilton Walk, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: delikatn@mail.med.upenn.edu.
authors.forename: E James
authors.initials: EJ
authors.lastname: Delikatny
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002797:Choline Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D006426:Hemicholinium 3 / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D049268:Positron-Emission Tomography; D011485:Protein Binding
chemical_list: D004791:Enzyme Inhibitors; D006426:Hemicholinium 3; D002797:Choline Kinase; D002798:Diacylglycerol Cholinephosphotransferase
keywords: Choline kinase; Inhibitors; Lipid metabolism; Tumor metabolism