Targeting Sphingosine Kinases for the Treatment of Cancer.

Sphingosine kinases (SK1 and SK2) are key, druggable targets within the sphingolipid metabolism pathway that promote tumor growth and pathologic inflammation. A variety of isozyme-selective and dual inhibitors of SK1 and SK2 have been described in the literature, and at least one compound has reached clinical testing in cancer patients. In this chapter, we will review the rationale for targeting SKs and summarize the preclinical and emerging clinical data for ABC294640 as the first-in-class selective inhibitor of SK2.