Targeted Expression of BikDD Eradicates Pancreatic Tumors in Noninvasive Imaging Models

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• 作者：Xiaoming Xie ; Weiya Xia ; Zhongkui Li ; Hsu-Ping Kuo ; Yuanfang Liu ; Zheng Li ; Qingqing Ding ; Su Zhang ; Bill Spohn ; Yan Yang ; Yongkun Wei ; Jing-Yu Lang ; Douglas B. Evans ; Paul J. Chiao ; James L. Abbruzze
• 关键词：CELLCYCLE
• 刊名：Cancer Cell
• 出版年：2007
• 出版时间：10 July 2007
• 年：2007
• 卷：12
• 期：1
• 页码：52-65
• 全文大小：1949 K

文摘

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.