RSPO1 and cancer: Rspo1 has been identified as a ligand for Lgr5 and an essential factor for activation of the Wnt signaling pathway.9,10 Using this 3D culture system, cancer and non-cancer organoids derived from human colon, prostate, pancreas, and liver have been established.6,11–14 We have also reported that inhibition of DNA methylation suppresses the growth of intestinal tumor organoids, and that when organoids derived from human intrahepatic cholangiocarcinomas are induced to differentiate to hepatocytes, their malignant potential is reduced.15,16