SPHK1 and hepatocellular carcinoma: Lastly, in addition to the approaches discussed above and given the complexity of molecular aberrancies in unresectable HCC, combining strategies to increase ceramide levels (e.g., rhASM) with those that prevent ceramide degradation (e.g., ceramidase inhibitors) and/or production of S1P (e.g., SPHK1 inhibitors) deserve additional consideration.