Targeting the lipids LPA and S1P and their signalling pathways to inhibit tumour progression.
The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), the enzymes that generate and degrade them, and the receptors that receive their signals are all potential therapeutic targets in cancer. LPA and S1P signalling pathways can modulate a range of cellular processes that contribute to tumourigenesis, such as proliferation and motility, and components of the signalling pathways often show aberrant expression and altered activity upon malignant transformation. This article reviews LPA- and S1P-mediated activities that might contribute to the aetiology of cancer, and examines the potential of the many antagonists that have been developed to inhibit LPA and S1P signalling pathways. In addition, the outcomes of various clinical trials using LPA- and S1P-associated targets in cancer and other diseases are described, and future directions are discussed.
Murph
Mandi
M
Department of Systems Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. mmmurph@mdanderson.org
Mills
Gordon B
GB
D018450:Disease Progression; D016503:Drug Delivery Systems; D008246:Lysophospholipids / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C032881:lysophosphatidic acid