The Current State of Cancer Gene Therapy and Its Application in Esophageal Carcinoma

Abstract

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. Conclusion: 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.

Effectiveness of HSV-tk Suicide Gene Therapy Driven by the Grp78 Stress-Inducible Promoter in Esophagogastric Junction and Gastric Adenocarcinomas

“…5 This study investigated and compared the in vitro and in vivo effectiveness of HSV-tk/GCV suicide gene therapy in gastroesophageal junction and gastric body adenocarcinomas. Very few gene therapy studies have been reported for junctional or esophageal adenocarcinoma, with esophageal cancer studies focusing on squamous cell carcinoma [6][7][8][9] and gastric cancer studies focusing on the non-junctional/ non-cardia gastric cancers. 8 The limited number of esophageal adenocarcinoma gene therapy studies have unfortunately mostly used inappropriate cell lines or animal models, reflecting the paucity of suitable models.…”