Downregulating sphingosine kinase-1 for cancer therapy

被引：12

作者：

Cuvillier, Olivier

机构：

[1] CNRS, UMR5089, Inst Pharmacol & Biol Struct, F-31077 Toulouse 4, France

[2] Univ Toulouse, Toulouse, France

来源：

EXPERT OPINION ON THERAPEUTIC TARGETS | 2008年 / 12卷 / 08期

关键词：

antagonists & inhibitors; ceramide; sphingolipids; sphingosine; sphingosine kinase-1; 1-phosphate;

D O I：

10.1517/14728222.12.8.1009

中图分类号：

R9 [药学];

学科分类号：

1007 [药学];

摘要：

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.

引用

收藏

页码：1009 / 1020

页数：12

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