Of spiders and crabs: the emergence of lysophospholipids and their metabolic pathways as targets for therapy in cancer.
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two small lysophospholipids, are potent inducers of many of the hallmarks of cancer including cell proliferation, survival, migration, invasion, and neovascularization in in vitro and in vivo tumor models. Furthermore, the enzymes metabolizing LPA and S1P and their receptors are aberrant in multiple cancer lineages and exhibit transforming activity altering patterns and targets for metastasis. Several recent studies show the remarkable activity of new chemical genomics and/or potential novel drugs in preclinical models. Combined with the physiologic and pathophysiologic activities of LPA and S1P, these studies suggest the implementation of preclinical and clinical evaluation of LPA and S1P as therapeutic targets.
Murph
Mandi
M
Department of Molecular Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Tanaka
Tamotsu
T
Liu
Shuying
S
Mills
Gordon B
GB
D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy*; D049368:Receptors, Lysophosphatidic Acid / Q000502:physiology; D049349:Receptors, Lysosphingolipid / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology
D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C032881:lysophosphatidic acid