The emerging role of FTY720 (Fingolimod) in cancer treatment

被引:126
作者
White, Christopher [1 ]
Alshaker, Heba [2 ,3 ]
Cooper, Colin [3 ]
Winkler, Matthias [4 ]
Pchejetski, Dmitri [3 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Sch Med, London, England
[2] Univ Petra, Fac Pharm & Med Sci, Dept Pharmacol & Biomed Sci, Amman, Jordan
[3] Univ E Anglia, Sch Med, Norwich NR4 7TJ, Norfolk, England
[4] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England
关键词
sphingolipid; sphingosine kinase; fingolimod; FTY720; cancer; SPHINGOSINE KINASE 1; PROTEIN PHOSPHATASE 2A; CHRONIC LYMPHOCYTIC-LEUKEMIA; RESISTANT PROSTATE-CANCER; ACUTE MYELOID-LEUKEMIA; TUMOR-SUPPRESSOR PP2A; CHRONIC INTESTINAL INFLAMMATION; CHRONIC MYELOGENOUS LEUKEMIA; CELLS IN-VITRO; BREAST-CANCER;
D O I
10.18632/oncotarget.7145
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
FTY720 (Fingolimod) is a clinically approved immunomodulating therapy for multiple sclerosis that sequesters T-cells to lymph nodes through functional antagonism of sphingosine-1-phosphate 1 receptor. FTY720 also demonstrates a proven efficacy in multiple in vitro and in vivo cancer models, suggesting a potential therapeutic role in cancer patients. A potential anticancer mechanism of FTY720 is through the inhibition of sphingosine kinase 1, a proto-oncogene with in vitro and clinical cancer association. In addition, FTY720's anticancer properties may be attributable to actions on several other molecular targets. This study focuses on reviewing the emerging evidence regarding the anticancer properties and molecular targets of FTY720. While the clinical transition of FTY720 is currently limited by its immune suppression effects, studies aiming at FTY720 delivery and release together with identifying its key synergetic combinations and relevant patient subsets may lead to its rapid introduction into the clinic.
引用
收藏
页码:23106 / 23127
页数:22
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