Sphingolipid metabolism and signaling as a target for cancer treatment

Sphingolipids play key roles in the régulation of several biological processes that are integral to cancer pathogenesis. Among the sphingolipid metabolites, ceramide and sphingosine-1-phosphate (S1P) have been shown to modulate cancer development and progression. The biological roles of other metabolites, such as sphingosine, and ceramide 1-phosphate, are also beginning to emerge. In general, ceramide plays a role as a tumor-suppressing lipid-inducing anti-proliferative response such as cell cycle arrest, induction of apoptosis, and senescence whereas S1P plays a role as a tumor-promoting lipid-inducing transformation, cellular proliferation, and inflammation in various cell models. Glycosphingolipids, another emerging class of bioactive sphingolipids, are believed to play anti-apop- totic roles and offer drug resistance to currently used chemotherapeutic drugs. These emerging biological roles of sphingolipids and its potential usefulness in treating cancer in the form of anticancer therapeutics are discussed in this chapter.