Pancreatic cancer is an aggressive malignancy with morbidity rates almost equal to mortality rates because of the current lack of effective treatment options. Here, we describe a targeted approach to treating pancreatic cancer with effective therapeutic efficacy and safety in noninvasive imaging models. We developed a versatile expression vector "VISA" (VP16-GAL4-WPRE integrated systemic amplifier) and a CCKAR (cholecystokinin type A receptor) gene-based, pancreatic-cancer-specific promoter VISA (CCKAR-VISA) composite to target transgene expression in pancreatic tumors in vivo. Targeted expression of BikDD, a potent proapoptotic gene driven by CCKAR-VISA, exhibited significant antitumor effects on pancreatic cancer and prolonged survival in multiple xenograft and syngeneic orthotopic mouse models of pancreatic tumors with virtually no toxicity.