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Abstract
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. Results/conclusion: 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.
Acknowledgements
The author would like to thank all past and present members of his laboratory and acknowledge the generous support of the Institut National de la Santé et de la Recherche Médicale (Inserm), Centre National de la Recherche Scientifique (CNRS), the Institut National du Cancer (INCa), the Association pour la Recherche sur le Cancer (ARC), the Ligue Nationale contre le Cancer, the Association pour la Recherche sur les Tumeurs de la Prostate (ARTP), the Association Française d'Urologie (AFU), and the Hôpitaux de Toulouse.