Furthermore, down-regulation of SphK1 activity by specific inhibitor PF-543 (Figure 3) led to induction of programmed necrosis in colorectal carcinoma cell lines HCT116, HT29 and DLD-1, primary cells derived from CRC patients and HCT-116 xenograft in SCID mice, which resulted in improved survival outcome in mice [67]. This evidence concerns the gene SPHK1 and colorectal carcinoma.