Sphingosine kinase inhibitors and cancer : seeking the gloden sword of Hercules
Cet article passe en revue les perspectives offertes par les inhibiteurs de sphingosine kinase pour le traitement des cancers
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 over-expression of the enzyme. Therefore, inhibitors of sphingosine kinase represent a novel class of compounds that have potential as anti-cancer 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 pharmacological and biochemical findings on sphingosine kinase into new drug discovery programmes for treatment of cancer.