Gene therapy in pancreatic cancer

Abstract

Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC.

Sporamin induces apoptosis and inhibits NF-κB activation in human pancreatic cancer cells

“…12,13 Inhibition of cell viability and proliferation activity could be attributable to the induction of cell apoptosis in PC cells. 12,13 Therefore, whether the cell growth suppression observed was induced by apoptosis was then examined.…”

“…12,13 Inhibition of cell viability and proliferation activity could be attributable to the induction of cell apoptosis in PC cells. 12,13 Therefore, whether the cell growth suppression observed was induced by apoptosis was then examined. In this study, treatment of PANC-1 and BxPC-3 cells with sporamin showed DNA fragmentation or nuclear condensation in the nucleus measured using DAPI staining, which is typically observed in apoptotic cells, and a significant increase in the percentage of apoptotic cells was confirmed by flow cytometer.…”

Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes

“…Unfortunately clinical results did not reflect those positively obtained in vitro [19,38,67,68,69,70]. A compound is now evaluated at the clinical stage, the LODER ® (Silenseed Ltd., Modi’in, Israel) that is a miniature biodegradable intratumoral implant containing and releasing within 4 months siRNA against Kras .…”

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

“…According to recent literatures, ErbB signaling pathway and TGF-beta signaling pathway participate in the transmembrane signal transduction of pancreatic cancer [13, 14]. Such transmembrane signal transduction pathways have been further validated to transfer the signals to intracellular pathways (such as p53 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and VEGF signaling pathway) [13, 15–17]. Intracellular signaling pathways have been identified to contribute to the abnormal proliferation of pancreatic cells and further initiate the tumorigenesis.…”