Despite the majority of CRCs having deactivating TGF‐β pathway mutations (TGFBR1, TGFBR2, SMAD4, SMAD2, SMAD3), colorectal tumours produce significant amounts of TGF‐β, creating a TGF‐β rich environment, to which only the stromal compartment can respond (Calon et al., 2012). This evidence concerns the gene SMAD3 and colorectal neoplasm.