SMAD4 and neoplasm: The present study revealed the molecular basis for SMAD4-dependent and -independent differences in PDAC tumor biology with the aim of identifying the subset of patients likely to respond to therapies targeting the TGF-β or EGFR signaling pathways (Figure 7) The use of model system illustrated here may help to identify additional nodes of therapeutic intervention in PDAC patients devoid of SMAD4.