The Role of Ceramide and Sphingolipid Metabolism in Cancer Therapeutics.

Abstract

Sphingolipids are a class of bioactive lipids which are highly involved in cellular functions such as signaling, membrane composition, and determining cell fate. The metabolism of these lipids plays important roles in the development and progression of many diseases such as cancer. The role of sphingolipid metabolism in cancer overall is not yet fully understood. However, key sphingolipids such as sphingosine-1-phosphate (S1P) and ceramide have been shown to be influential on the death or survival of cancer cells. S1P is known to exert pro-survival signaling effects when expressed at higher levels in cells. Ceramide, on the other hand, has been established as a pro-death lipid, regulating apoptosis, cell cycle arrest, autophagy, and mitophagy. Cancer cells are typically characterized by an increased ratio in S1P to ceramide, thus granting the survival of the cancer. This ceramide/S1P biostat is the target of many new therapeutics which aim to increase ceramide levels in cancer cells. Additionally, many previously established drugs have been rediscovered for their unexpected ability to perturb sphingolipid metabolism. This review serves to summarize the current use of ceramide and sphingolipid metabolism-related therapies for the treatment of many cancers.