Regulation of cellular sphingosine-1-phosphate by sphingosine kinase 1 and sphingosine-1-phopshate lyase determines chemotherapy resistance in gastroesophageal cancer

Table 2 SPHK1 and S1P inhibitors in clinical development as anti-cancer therapies

Agent	Mechanism	Stage of Clinical Development	References
Safingol	SPHK1 inhibitor	Demonstrated safety in combination with cisplatin in Phase I trial in solid tumours	[43, 46, 47]
Fingolimod	S1P receptor antagonist	Licenced for use in multiple sclerosis. No data on clinical use in cancer	[29, 30, 44]
(FTY720)	S1P receptor antagonist		[29, 30, 44]
Sonepcizumab	Humanised S1P neutralising monoclonal antibody	Demonstrated safety in Phase I trial in solid tumours	[48, 49]
(LT1009)	Humanised S1P neutralising monoclonal antibody	Demonstrated safety in Phase I trial in solid tumours	[48, 49]