We now report that simultaneous suppression of both pathways attenuated colony formation of ASPC-1 human pancreatic cancer cells grown in 3-D culture and tumor growth in vivo, but targeting TGF-β reversed the growth-inhibitory effects exerted by EGFR silencing in T3M4 human pancreatic cancer cells, and this reversal occurred in conjunction with src activation as reflected by increased src phosphorylation on tyrosine 419. Here, EGFR is linked to familial pancreatic carcinoma.