Gene therapy developments for pancreatic cancer

Bhattacharyya, Madhumita; Lemoine, Nick R.

doi:10.1016/j.bpg.2005.10.004

Cited by 34 publications

(30 citation statements)

References 47 publications

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“…Strategies for gene therapy in pancreatic cancer include antisense and RNA interference strategies whereby the function of activated oncogenes (K-ras, H-ras, Notch, LSM1, etc) is inhibited, and strategies to restore the function of tumor suppressor genes (p53, p16, p21, Smad4, etc). These therapeutic strategies have shown their promising effects on the inhibition of pancreatic cancer in vitro and in vivo (Bhattacharyya and Lemoine, 2006). In addition, gene-directed pro-drug activation therapy is another gene therapy system in which a gene that encodes an enzyme is delivered to tumor cell.…”

Section: Using Gene Therapy To Enhance Cancer Chemotherapeutic Efficacymentioning

confidence: 99%

Pancreatic cancer: Pathogenesis, prevention and treatment

Sarkar

Banerjee

2007

Toxicology and Applied Pharmacology

104

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Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-κB pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-κB, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer.

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Section: Using Gene Therapy To Enhance Cancer Chemotherapeutic Efficacymentioning

confidence: 99%

Pancreatic cancer: Pathogenesis, prevention and treatment

Sarkar

Banerjee

2007

Toxicology and Applied Pharmacology

104

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“…4,5 Therefore, new strategies for pancreatic cancer, such as molecular target therapies and gene therapies, are needed and beginning to show remarkable promise. 6,7 Although adenovirus-mediated gene therapy is one of the promising approaches for cancer treatment because of the high transduction efficiency, 8 the great results demonstrated at the laboratory level are not always obtained in clinical settings. 9 Therefore, it is still necessary to develop devices for improving the efficiency of the gene introduction.…”

Section: Introductionmentioning

confidence: 99%

Gemcitabine synergistically enhances the effect of adenovirus gene therapy through activation of the CMV promoter in pancreatic cancer cells

et al. 2010

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Adenovirus-mediated gene therapy shows remarkable promise as a new strategy for advanced pancreatic cancer, but satisfactory clinical results have not yet been obtained. To improve this gene therapy, we investigated the effects of gemcitabine (GEM) on transgene expression by adenoviral vectors and their biological effects. We used Ad-lacZ and adenoviral vector-expressing NK4 (Ad-NK4) as representative adenoviral vectors. These vectors express b-galactosidase (b-gal) and NK4 (which inhibits the invasion of cancer cells), respectively, under the control of the CMV promoter. Cells were infected with the individual adenoviruses and then treated with GEM. GEM increased b-gal mRNA expression and b-gal activity, and increased NK4 expression in both culture media and within infected cells, in dose-dependent manners. The increased expression of NK4 delivered by Ad-NK4 had biological effects by inhibiting the invasion of cancer cells. GEM also enhanced NK4 expression in SUIT-2 cells transfected with an NK4-expressing plasmid, suggesting that GEM enhanced CMV promoter activity. In in vivo experiments, NK4 expression within subcutaneously implanted tumors was increased in GEM-treated mice compared with control mice. These results suggest that adenovirus-mediated gene therapy with GEM may be a promising approach for treating pancreatic cancer, and that this combination therapy may decrease the risks of side effects.

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“…These have included the replacement of tumor suppressor genes (TP53, CDKN2A), the inactivation of oncogenes (KRAS) and targeting of apoptotic and angiogenic pathways. 7 However, finding efficient gene delivery tools remains an enormous challenge. In this study, we set out to assess the potential of lentivectors for gene delivery to pancreatic cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…With respect to gene therapy approaches for pancreatic cancer, a variety of gene delivery methods as well as intracellular targets have been explored. [7][8][9] Our own experience has been with adenoviral vectors, which showed efficient gene delivery to pancreatic cancer cells. 10,11 However, for this vector type to be used in humans, barriers such as pre-existing immunity and shortlived expression need to be overcome.…”

Section: Introductionmentioning

confidence: 99%