The resulting topology integrates centrally involved proteins of the common signaling pathways and generally accepted cancer drivers in CRC—such as APC, p53m, KRAS, DCC, TGFβR, PTEN and SMAD4 allowing a simplified view on the progression from normal cells to tumor cells (Table A2, Figure A8) [2,40,41,42]. This evidence concerns the gene SMAD4 and cancer.