title: PDX1 associated therapy in translational medicine.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis and a low median survival due to lack of the early and reliable detection and effective therapeutic options, despite improvements observed for many other cancers in last decade. Pancreatic and duodenal homeobox 1 (PDX1), which is a homeodomain-containing transcription factor and a key regulator for insulin gene expression, β cell maturation and proper β cell function maintenance in the pancreas. Our previous studies revealed that PDX1 promotes tumorigenesis and it is a promising therapeutic target for PDAC. For translational purposes, we developed three therapeutic platforms utilizing RNA interference (RNAi), gene therapy and small inhibitory drug targeting PDX1, and further validated them in PDAC preclinical models both in vitro and in vivo. These PDX1 targeted therapies significantly inhibited PDX1 expression in PDAC cells, ablated PDX1-expressing human PDAC xenograft tumor growth, and prolonged survival in the PDAC mouse models. The data from these preclinical studies proved the translational potentials of PDX1 targeted therapies in PDAC and suggest that the strategy of developing PDX1 targeted therapies would permit a rapid bench-to-bedside translation of other relevant gene therapies, which would eventually benefit the patients suffering from this deadly disease.
authors.affiliation: 1 Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; 2 Mary Crowley Cancer Research Center, Dallas, TX, USA ; 3 Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Juehua
authors.initials: J
authors.lastname: Yu
authors.affiliation: 1 Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; 2 Mary Crowley Cancer Research Center, Dallas, TX, USA ; 3 Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Shi-He
authors.initials: SH
authors.lastname: Liu
authors.affiliation: 1 Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; 2 Mary Crowley Cancer Research Center, Dallas, TX, USA ; 3 Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Robbi
authors.initials: R
authors.lastname: Sanchez
authors.affiliation: 1 Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; 2 Mary Crowley Cancer Research Center, Dallas, TX, USA ; 3 Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.affiliation: 1 Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; 2 Mary Crowley Cancer Research Center, Dallas, TX, USA ; 3 Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Rozengurt
authors.affiliation: 1 Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; 2 Mary Crowley Cancer Research Center, Dallas, TX, USA ; 3 Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: F Charles
authors.initials: FC
authors.lastname: Brunicardi
keywords: Pancreatic and duodenal homeobox 1 (PDX1); RIP-TK; RNA interference (RNAi); metformin; pancreatic cancer