SMAD4 and colorectal carcinoma: Molecular genetic studies have revealed that genetic alterations in driver genes induce the development of colorectal cancer (CRC) through an adenoma carcinoma sequence.1, 2, 3 It has recently been demonstrated that cumulative mutations in APC, KRAS, SMAD4 and TP53 in human intestinal cell-derived organoids are associated with the development of transplanted tumors in immunodeficient mice.4, 5 However, despite these findings, the precise functional role of each driver gene mutation in the malignant progression is still not fully understood.