KRAS and colorectal carcinoma: The sequential introduction of CRC driver gene alterations affecting the aforementioned signaling pathways (oncogenic mutations in KRAS and PIK3CA and disruption of APC, TP53 and SMAD4 tumor suppressor genes) into normal human organoids using CRISPR-Cas9 allowed the modelling of the adenoma-carcinoma progression upon transplantation into mice [43,44,55].