Targeting sphingolipid metabolism in head and neck cancer: rational therapeutic potentials.

IMPORTANCE OF THE FIELD: Ceramide accumulation has been shown to be a conserved mechanism of apoptosis initiation in normal physiological processes as well as in response to cancer treatments. Therefore, it is unsurprising that many cancers develop aberrations of sphingolipid metabolism that prevent the accumulation of ceramide, whether by reduction of ceramide generation or by enhanced ceramide catabolism, particularly dangerous when catabolism leads to generation of pro-tumor sphingosine-1-phosphate and ceramide-1-phosphate. Numerous studies have now implicated dysregulation of sphingolipid metabolism in head and neck cancers. AREAS COVERED IN THIS REVIEW: This review highlights the importance of sphingolipid metabolism and brings sphingolipid metabolism to the forefront in the investigation of novel therapies for head and neck cancer. It reviews sphingolipid-centric therapies under investigation in preclinical and clinical trials of cancers of the head and neck. WHAT THE READER WILL GAIN: The roles of sphingolipids and sphingolipid metabolism in cancer are reviewed and the reader will be brought up to date with discoveries in the field of sphingolipid metabolism in head and neck cancer. TAKE HOME MESSAGE: As treatments for head and neck cancers are currently limited, the potential of targeting sphingolipid metabolism should be taken into consideration as we seek novel ways to combat this group of tumors.