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Sphingosine kinase inhibitors and cancer : seeking the golden sword of Hercules

Pyne, Susan and Bittman, Robert and Pyne, Nigel (2011) Sphingosine kinase inhibitors and cancer : seeking the golden sword of Hercules. Cancer Research, 71 (21). pp. 6576-6582. ISSN 0008-5472

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There is considerable evidence that sphingosine kinases play a key role in cancer progression, which might involve positive selection of cancer cells that have been provided with a survival and growth advantage as a consequence of overexpression of the enzyme. Therefore, inhibitors of sphingosine kinase represent a novel class of compounds that have potential as anticancer agents. Poor inhibitor potency is a major issue that has precluded successful translation of these compounds into the clinic. However, recent discoveries have shown that sphingosine kinase 1 is an allosteric enzyme and that some inhibitors offer improved effectiveness by inducing proteasomal degradation of the enzyme or having nanomolar potency. Herein, we provide a perspective about these recent developments and highlight the importance of translating basic pharmacologic and biochemical findings on sphingosine kinase into new drug discovery programs for treatment of cancer.