Combining Apc mutations with deletions of the TGF-β signaling mediators Smad3, Smad4 or Smad3/4 in double, triple or cell-specific LoxP/Cre knockout mice further accelerates tumor formation but the majority of tumors continue to arise predominantly in the small intestine (Neto et al, 2023; Bürtin et al, 2020). This evidence concerns the gene APC and neoplasm.