We previously identified SphK1/S1P signaling as a new modulator of HIF-1α activity under hypoxia owing to a decreased proteasome degradation of HIF-1α subunit mediated by the Akt/GSK3β pathway in various cancer cell models.32 More recently, we reported in a prostate cancer animal model that sphingomab, a monoclonal antibody neutralizing extracellular S1P, could reduce hypoxia and associated vascular network malfunction by interfering with HIF-1 activity thus enhancing delivery and efficacy of docetaxel, the standard chemotherapy.24 The gene discussed is SPHK1; the disease is cancer.