Choline kinase as a precision medicine target for therapy in cancer, autoimmune diseases and malaria

Cancer cells have an altered metabolism that provides advantages to support unregulated growth and higher duplication rates. Among these critical changes, energy generation through aerobic glycolysis as well as increased glutamine catabolism, are essential components associated with altered levels of specific metabolites. Up-regulation of lipid metabolism also occurs frequently in cancer cells. Increased fatty-acid biosynthesis as well as their elongation and saturation processes are among widely recognized events that define cancer cells. Not surprisingly, the CDP-choline and CDP-ethanolamine pathways responsible for the generation of membrane phospholipids is a major alteration frequently found in human tumours. Choline kinase a (ChoKa) plays a critical role in this latter metabolic route and is the focus of a targeted therapeutic strategy. Small molecule inhibitors of this enzyme are effective and selective anticancer drugs that have recently entered clinical trials. More recently, ChoKa inhibitors have been proposed as a novel therapeutic approach against malaria and rheumatoid arthritis. Here, the evidence that support the use of ChoKa as a novel drug target for precision medicine approaches is discussed.