Downregulating sphingosine kinase-1 for cancer therapy.
BACKGROUND
The sphingolipids ceramide and sphingosine 1-phosphate (S1P) are key regulators of cell death and proliferation. The subtle balance between their intracellular levels is governed mainly by sphingosine kinase-1, which produces the pro-survival S1P. Sphingosine kinase-1 is an oncogene; is overexpressed in many tumors; protects cancer cells from apoptosis in vitro and in vivo; and its activity is decreased by anticancer therapies. Hence, sphingosine kinase-1 appears to be a target of interest for therapeutic manipulation.


OBJECTIVE
This review considers recent developments regarding the involvement of sphingosine kinase-1 as a therapeutic target for cancer, and describes the pharmacological tools currently available.


CONCLUSIONS
The studies described provide strong evidence that strategies to kill cancer cells via sphingosine kinase-1 inhibition are valid and could have a favorable therapeutic index.
Cuvillier
Olivier
O
Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex 4, France. olivier.cuvillier@ipbs.fr
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation; D000099157:Sphingosine Kinase
D000970:Antineoplastic Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase