Koert F D Kuhlmann1, Dirk J Gouma, John G Wesseling. 1. Department of Surgery, AMC Liver Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. k.f.kuhlmann@amc.uva.nl
Abstract
BACKGROUND: The prognosis of patients with pancreatic cancer is poor. This is mainly caused by the late diagnosis, the aggressive biology and the lack of effective treatment modalities. Adenoviral gene therapy has the potential to selectively treat both primary tumor and (micro)metastatic tissue. METHODS: This review provides an overview of what has been achieved so far in the field of adenoviral gene therapy for pancreatic cancer. RESULTS: Transductional targeting allows decreased toxicity due to vector dissemination to non-target cells and permits delivery with a lower viral dose. It can evade or diminish the immune response, which remains a major problem. Transcriptional targeting evolves quickly but essential drawbacks such as the lack of an efficient animal model delay clinical application. Few clinical trials utilizing adenoviruses have been performed in patients with pancreatic cancer today. Worldwide, only seven phase III trials are being performed investigating adenoviral vectors in cancer patients. CONCLUSION: A clear therapeutic effect of adenoviral gene therapy in pancreatic cancer has not yet been achieved, because the step from bench to bedside has encountered drawbacks. Combinations of the different targeting strategies and techniques to evade the immune system harbor the future for adenoviral gene therapy in patients with pancreatic cancer. Copyright 2008 S. Karger AG, Basel.
BACKGROUND: The prognosis of patients with pancreatic cancer is poor. This is mainly caused by the late diagnosis, the aggressive biology and the lack of effective treatment modalities. Adenoviral gene therapy has the potential to selectively treat both primary tumor and (micro)metastatic tissue. METHODS: This review provides an overview of what has been achieved so far in the field of adenoviral gene therapy for pancreatic cancer. RESULTS: Transductional targeting allows decreased toxicity due to vector dissemination to non-target cells and permits delivery with a lower viral dose. It can evade or diminish the immune response, which remains a major problem. Transcriptional targeting evolves quickly but essential drawbacks such as the lack of an efficient animal model delay clinical application. Few clinical trials utilizing adenoviruses have been performed in patients with pancreatic cancer today. Worldwide, only seven phase III trials are being performed investigating adenoviral vectors in cancerpatients. CONCLUSION: A clear therapeutic effect of adenoviral gene therapy in pancreatic cancer has not yet been achieved, because the step from bench to bedside has encountered drawbacks. Combinations of the different targeting strategies and techniques to evade the immune system harbor the future for adenoviral gene therapy in patients with pancreatic cancer. Copyright 2008 S. Karger AG, Basel.
Authors: Shi-He Liu; Nancy Smyth-Templeton; Alan R Davis; Elizabeth A Davis; Nikiforos Ballian; Min Li; Hao Liu; William Fisher; F Charles Brunicardi Journal: Surgery Date: 2011-02-05 Impact factor: 3.982
Authors: Andrea M Murphy; Dahlia M Besmer; Megan Moerdyk-Schauwecker; Natascha Moestl; David A Ornelles; Pinku Mukherjee; Valery Z Grdzelishvili Journal: J Virol Date: 2012-01-11 Impact factor: 5.103