title: Therapeutic potential of targeting sphingosine kinase 1 in prostate cancer.
abstract: Sphingosine kinase 1 (SK1) is a lipid enzyme with oncogenic properties that converts the proapoptotic lipid sphingosine into the antiapoptotic lipid sphingosine-1-phosphate, which activates the signal transduction pathways that lead to cell proliferation, migration, activation of the inflammatory response and impairment of apoptosis. Compelling evidence suggests that SK1 activation contributes to cancer progression leading to increased oncogenic transformation, tumor growth, resistance to therapies, tumor neovascularization and metastatic spread. High levels of SK1 expression or activity have been associated with poor prognosis in several cancers, including those of the prostate. Recent studies using prostate cancer cell and mouse models demonstrate a significant potential for SK1-targeting therapies to synergize with the effects of docetaxel chemotherapy and radiotherapy. However, until recently the absence of clinically applicable SK1 inhibitors has limited the translation of these findings into patients. With the recent discovery that clinically approved drug fingolimod has SK1-inhibiting properties, SK1 has gained significant attention from both clinicians and the pharmaceutical industry and it is hoped that trials of newly developed SK1 inhibitors might follow soon.
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, 807 Cyclotron Building, Hammersmith Hospital, Du Cane road, London W12 0NN, UK. d.pshezhetskiy@ imperial.ac.uk
authors.forename: Dmitri
authors.initials: D
authors.lastname: Pchejetski
authors.forename: Torsten
authors.initials: T
authors.lastname: Böhler
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Jonathan
authors.initials: J
authors.lastname: Waxman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D006801:Humans; D008297:Male; D051379:Mice; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000502:physiology; D011409:Propylene Glycols / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000209:etiology; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000099157:Sphingosine Kinase
chemical_list: D000068876:Fingolimod Hydrochloride; D017853:Phosphotransferases (Alcohol Group Acceptor); D011409:Propylene Glycols; D013110:Sphingosine; D000099157:Sphingosine Kinase