SPHK1 and cancer: Regarding the bioactive lipid S1P, its neutralizing monoclonal antibody, sphingomab, has proven to be effective at inhibiting angiogenesis, tumor growth and metastasis in multiple cancer cell lines.107 Similar effects on cancer progression have been observed with inhibitors of its upstream regulatory sphingosine kinase 1 (SphK1)144 or its receptor (S1P receptor 1).145 Moreover, sphingomab increases the sensitivity of RCC-bearing mice to sunitinib treatment, which inhibits VEGFR2 tyrosine kinase.146 Hence, sphingomab constitutes a promising therapy for RCC non-responder patients.