Targeted expression of BikDD eradicates pancreatic tumors in noninvasive imaging models.
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.
Xie
Xiaoming
X
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Xia
Weiya
W
Li
Zhongkui
Z
Kuo
Hsu-Ping
HP
Liu
Yuanfang
Y
Li
Zheng
Z
Ding
Qingqing
Q
Zhang
Su
S
Spohn
Bill
B
Yang
Yan
Y
Wei
Yongkun
Y
Lang
Jing-Yu
JY
Evans
Douglas B
DB
Chiao
Paul J
PJ
Abbruzzese
James L
JL
Hung
Mien-Chie
MC
D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011949:Receptors, Cholecystokinin / Q000235:genetics; D019076:Transgenes
D011949:Receptors, Cholecystokinin