Buskens Christianne J, Marsman Willem A, Bosma Piter J, van Lanschot J Jan B
Department of Surgery, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Dig Surg. 2005;22(4):222-33. doi: 10.1159/000088052. Epub 2005 Sep 20.
Advances in molecular genetics have accelerated the understanding of the genetic basis of many diseases. This is particularly true for esophageal adenocarcinoma with its well-defined premalignant lesions. At the same time, remarkable progress in recombinant DNA technology has enabled the development of molecular treatments for inherited disorders, infectious diseases and cancer. In recent years, especially the development of gene therapy systems as new treatment or prevention strategies for various malignant diseases has been explored. The present article deals with the general principles of gene therapy and then focuses on how these principles can be applied to esophageal cancer. Subsequently, the scarcely available experimental data from the literature are briefly reviewed. Finally, we summarize our experimental work over the last few years. Our main goal has been to develop an efficient and selective gene delivery system in order to maximize the proportion of successfully transduced tumor cells while sparing normal cells.
The field of cancer gene therapy has evolved tremendously, with promising developments especially in the field of targeting and novel therapeutic genes. However, substantial research is still needed before gene therapy can play a significant role in the management of esophageal cancer. The focus of this research should be on further developing adequate experimental models as well as on improving gene-delivering vectors. Although it is unlikely that cancer gene therapy will replace the conventional methods of treatment, selective and efficient vectors may be used for patients with Barrett's esophagus or as adjuvant therapy for patients with esophageal cancer in the future.
分子遗传学的进展加速了对许多疾病遗传基础的理解。对于具有明确癌前病变的食管腺癌来说尤其如此。与此同时，重组DNA技术取得了显著进展，使得针对遗传性疾病、传染病和癌症的分子治疗得以发展。近年来，人们尤其探索了基因治疗系统作为各种恶性疾病新的治疗或预防策略的发展情况。本文论述了基因治疗的一般原则，然后重点探讨了这些原则如何应用于食管癌。随后，简要回顾了文献中稀少的实验数据。最后，我们总结了过去几年的实验工作。我们的主要目标是开发一种高效且选择性的基因传递系统，以便在使正常细胞免受影响的同时，最大限度地提高成功转导肿瘤细胞的比例。
癌症基因治疗领域已经取得了巨大进展，尤其是在靶向和新型治疗基因领域有很有前景的发展。然而，在基因治疗能够在食管癌治疗中发挥重要作用之前，仍需要大量研究。这项研究的重点应该是进一步开发合适的实验模型以及改进基因传递载体。虽然癌症基因治疗不太可能取代传统治疗方法，但选择性和高效的载体未来可能用于巴雷特食管患者或作为食管癌患者的辅助治疗。
