Although SphK/S1P modulators may be promising treatment options, a potential problem with targeting SphK/S1P in pancreatic cancer is the fact that SphK1/S1P is necessary for the survival of the pancreatic cells; loss of SphK1 is linked to pancreatic beta-cell death and predisposition of diet-induced diabetes types 1 and 2 [197,198,199]. This evidence concerns the gene SPHK1 and familial pancreatic carcinoma.