title: The antineoplastic properties of FTY720: evidence for the repurposing of fingolimod.
abstract: Almost all drugs approved for use in humans possess potentially beneficial 'off-target' effects in addition to their principal activity. In some cases this has allowed for the relatively rapid repurposing of drugs for other indications. In this review we focus on the potential for re-purposing FTY720 (also known as fingolimod, Gilenya(™)), an immunomodulatory drug recently approved for the treatment of multiple sclerosis (MS). The therapeutic benefit of FTY720 in MS is largely attributed to the immunosuppressive effects that result from its modulation of sphingosine 1-phosphate receptor signalling. However, this drug has also been shown to inhibit other cancer-associated signal transduction pathways in part because of its structural similarity to sphingosine, and consequently shows efficacy as an anti-cancer agent both in vitro and in vivo. Here, we review the effects of FTY720 on signal transduction pathways and cancer-related cellular processes, and discuss its potential use as an anti-cancer drug.
authors.affiliation: Department of Oral Biology and Biomedical Sciences and Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sathya Narayanan
authors.initials: SN
authors.lastname: Patmanathan
authors.affiliation: Department of Oral Biology and Biomedical Sciences and Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lee Fah
authors.initials: LF
authors.lastname: Yap
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
authors.affiliation: Department of Oral Biology and Biomedical Sciences and Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Paterson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D058492:Drug Repositioning; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology*; D006801:Humans; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000068876:Fingolimod Hydrochloride
keywords: FTY720; S1P; apoptosis; cancer; cytotoxicity; fingolimod; sphingosine analogue