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Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Clin+Cancer+Res 2015 ; 21 (22): 5008-12 Nephropedia Template TP
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Molecular Pathways: Targeting Diacylglycerol Kinase Alpha in Cancer #MMPMID26420856
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Clin Cancer Res 2015[Nov]; 21 (22): 5008-12 PMID26420856show ga
Lipid kinases have largely been neglected as targets in cancer, and an increasing number of reports suggest diacylglycerol kinase alpha (DGK?) may be one with promising therapeutic potential. DGK? is one of ten DGK family members that convert diacylglycerol (DAG) to phosphatidic acid (PA), and both DAG and PA are critical lipid second messengers in the plasma membrane. A host of important oncogenic proteins and pathways affect cancer cells in part through DGK?, including the c-Met and VEGF receptors. Others partially mediate the effects of DGK? inhibition in cancer, such as mTOR and HIF-1?. DGK? inhibition can directly impair cancer cell viability, inhibits angiogenesis, and notably may also boost T cell activation and enhance cancer immunotherapies. While two structurally similar inhibitors of DGK? were established decades ago, they have seen minimal in vivo usage and it is unlikely that either of these older DGK? inhibitors will have utility for cancer. An abandoned compound that also inhibits serotonin receptors may have more translational potential as a DGK? inhibitor, but more potent and specific DGK? inhibitors are sorely needed. Other DGK family members may also provide therapeutic targets in cancer, but require further investigation.
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Clin+Cancer+Res 2015 ; 21 (22): 5008-12
