Engineered organoids, harbouring cooperating driver-mutations in key CRC pathways (Wnt, EGFR, p53, TGFβ, and/or PI3K), recapitulate the adenoma-carcinoma transition and exhibit a progressive loss of niche dependence, which confers a growth advantage in a hostile milieu [332,333,334,335]. This evidence concerns the gene TGFB1 and colorectal carcinoma.