Kuhlmann Koert F D, Gouma Dirk J, Wesseling John G
Department of Surgery, AMC Liver Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Dig Surg. 2008;25(4):278-92. doi: 10.1159/000145981. Epub 2008 Jul 17.
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.
This review provides an overview of what has been achieved so far in the field of adenoviral gene therapy for pancreatic cancer.
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.
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.
胰腺癌患者的预后较差。这主要是由诊断延迟、侵袭性生物学行为以及缺乏有效的治疗方式所致。腺病毒基因治疗有潜力选择性地治疗原发性肿瘤和（微）转移组织。
本综述概述了目前在胰腺癌腺病毒基因治疗领域已取得的成果。
转导靶向可降低因载体扩散至非靶细胞而产生的毒性，并允许以较低病毒剂量进行递送。它能够规避或减弱免疫反应，而免疫反应仍是一个主要问题。转录靶向发展迅速，但诸如缺乏高效动物模型等关键缺陷延缓了其临床应用。如今，在胰腺癌患者中开展的利用腺病毒的临床试验较少。在全球范围内，仅有七项III期试验正在研究癌症患者中的腺病毒载体。
腺病毒基因治疗在胰腺癌中尚未取得明确的治疗效果，因为从实验室到临床的过程中遇到了诸多缺陷。不同靶向策略与规避免疫系统技术的联合应用为胰腺癌患者的腺病毒基因治疗带来了未来的希望。
