Choline metabolism-based molecular diagnosis of cancer: an update.
Abnormal choline metabolism continues to be identified in multiple cancers. Molecular causes of abnormal choline metabolism are changes in choline kinase-α, ethanolamine kinase-α, phosphatidylcholine-specific phospholipase C and -D and glycerophosphocholine phosphodiesterases, as well as several choline transporters. The net outcome of these enzymatic changes is an increase in phosphocholine and total choline (tCho) and, in some cancers, a relative decrease of glycerophosphocholine. The increased tCho signal detected by (1)H magnetic resonance spectroscopy is being evaluated as a diagnostic marker in multiple cancers. Increased expression and activity of choline transporters and choline kinase-α have spurred the development of radiolabeled choline analogs as PET imaging tracers. Both tCho (1)H magnetic resonance spectroscopy and choline PET are being investigated to detect response to treatment. Enzymes mediating the abnormal choline metabolism are being explored as targets for cancer therapy. This review highlights recent molecular, therapeutic and clinical advances in choline metabolism in cancer.
The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, Baltimore, MD, USA.
Kristine
K
Glunde
Marie-France
MF
Penet
Lu
L
Jiang
Michael A
MA
Jacobs
Zaver M
ZM
Bhujwalla
D000818:Animals; D002794:Choline / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000379:methods; D006801:Humans; D053858:Metabolic Networks and Pathways; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy
D002794:Choline
GDPD5; GDPD6; cancer; choline kinase-α; choline metabolism; choline transporters; phospholipase C; phospholipase D; targeting; treatment strategy