Even an overwhelming amount of data indicate that increased S1P levels were associated with cancer progression, many recent reports showed disconcerting results: (i) in patients with hepatocellular carcinoma, a decrease in S1P levels in HCC tissue was linked to less tumor differentiation and more microvascular invasion (57); (ii) specific inhibition of SphK1 in 1483 head and neck carcinoma cells with PF-543 did not affect cell proliferation or survival (84), and (iii) pharmacological and molecular inhibition of SphK1 and SphK2 did not affect tumor cell growth, both in vitro and in vivo (85). The gene discussed is SPHK1; the disease is cancer.