Here we report that GCV increases the cellular killing effect of the minimal RB responsive-based selective adenovirus armed with the TK gene (ICOVIR15-TKT), inducing significantly higher antitumor response than the potent oncolytic ICOVIR15 upon intraductal delivery in two different xenograft models of human pancreatic cancer BxPC-3-Luc and PANC-1-Luc. This evidence concerns the gene RB1 and familial pancreatic carcinoma.