Preclinical studies have demonstrated that the selective SphK2 inhibitor ABC294640 not only inhibits tumor growth as a monotherapy by downregulating the MAPK/ERK signaling pathway but also synergistically reduces phosphorylated ERK (p-ERK) levels when combined with the multikinase inhibitor sorafenib, enhancing pro-apoptotic effects and delaying tumor progression (39). This evidence concerns the gene SPHK2 and neoplasm.