SMAD4 and colorectal carcinoma: Matano et al. (Matano et al., 2015) used CRISPR - Cas9 gene-editing technology to mutate a series of tumor suppressor genes APC, Smad4, TP53, and oncogenes KRAS, PI3K in normal epithelial organs, and produced corresponding CRC organoids via selective culture in medium without corresponding growth factors.