Does Fingolimod have anticancer effects? A meta-analysis and systematic review based on experimental animal models of various cancers

Abstract

Background: Numerous studies have explored the anticancer effect of FTY720 (Fingolimod) in animal models, a sphingosine-1-phosphate (S1P) receptor antagonist and an immunosuppressant, but little clinical evidence guides the use of FTY720 in cancer patients.Methods: Strictly, only related published articles about the treatment with FTY720 for various cancers in vivo from January 1998 to January 2020 were selected from PubMed, Web of Science, Ovid, Embase, CNKI and Cochrane databases, and which were qualified. We acquired agreement through discussion. Then, we conducted meta-analysis, subgroups analysis, publication bias analysis and sensitivity analysis based on selected studies. In the last two sections, we summaried and compared side effects, drug combination effects and molecular pathways from selected studies.Results: In the 31 articles included from 2002 to 2019, FTY720 was found to reduce tumor volume (SMD =-2.58, 95% CI: -3.42, -1.75, Z = 6.09, P = 0.000), tumor weight (SMD = -3.69, 95% CI: -5.17, -2.21, Z = 4.88, P = 0.000) and body weight (SMD = -0.86, 95% CI: -1.61, -0.11, Z = 2.23, P = 0.025) in 14 types of cancer. Relevant frequent signal pathways include the Akt pathway, S1PRs-Caspase pathway and the STAT3-PP2A pathway. FTY720 has significant independent or in combination anticancer effects and a lower toxicity in renal cell carcinoma and neuroblastoma mice models. However, it should be noted that FTY720 achieved a significant therapeutic effect in immunodeficient mice, not in immunecompetent mice. Also, the dosage-safety of FTY720 alone in clinical use is a noteworthy issue. In mouse models, the mechanism of the FTY720 treatment of tumors lies in inducing the tumor cells apoptosis through important signaling moleculars.Conclusions: FTY720 alone or in combination exerted significant anti-tumor effects for neuroblastoma and renal cell carcinoma, however not for melanoma. Due to insufficient evidence, more specific studies of FTY720 only and in combination included in immunity, inflammation and melanoma should be carried out in the future preclinical and clinical studies.