Current gene therapy for stomach carcinoma.

Abstract

Gastric cancer is common in China[1-42], and its early diagnosis and treatment in advanced stage are difficult[31-50]. In recent years, gene study in cancer is a hotspot, and great progress has been achieved[41-80]. Cancer gene therapy has shifted from the imagination into the laboratory and clinical trials. The “logic of how genes function” coupled with the connections of cell cycle processes to specific gene actions is creating a promise of treating tumors by gene therapy. There have been significant advances against both local and metastatic growths. The potential role of gene intervention extends from diseases caused by single gene defects, through severe viral infections, to polygenic disorders, such as diabetes mellitus and arteriosclerosis. However, gene therapy can be defined as the introduction and expression of an exogenous gene into human cells for therapeutic benefit, and is conventionally restricted to human diseases associated with single gene defects. The rapid progress in our understanding of some of the molecular mechanisms involved in the pathogenesis of cancer and metabolic disorders, with the development of gene delivery vector technology, has urged us to consider novel gene approaches to digestive diseases. There is no shortage of ideas and applications for gene intervention in human diseases, but there are great limitations not only with the efficiency and targeting of the present generation of gene transfer vectors but also with our incomplete understanding of transcription control[1,2]. The graduation of gene therapy from unfulfilled dreams to conventional therapy for gene and acquired disorders will require a mastery of multiple disparate components including gene delivery vectors, regulated tissue-specific gene expression, control of immunity and manipulation of cell viability. Improvement in suicide genes has opened up a whole new treatment modality for treating hyperproliferative disorders and for designing animal models for disease[3]. Along with herpes simplex virus-1 thymidine kinase, a host of additional suicide gene has been developed. A critical comparison of these will follow along with progress in utilizing these reagents for therapeutic benefits[81-90]. The current delineation of the molecular basis of cancer provides a strong rationale to consider gene therapy approaches for cancer as a complement to other cancer therapies. Phase III trials focused on adenoviral vector-mediated delivery of wild-type p53 to compliment p53 mutations were recently initiated for head and neck cancer and ovarian cancer. Clinical testing of the tumor inhibitory gene E1A, delivered by synthetic vectors is ongoing. Positive clinical data from these clinical studies will establish the use of gene therapy as a component of the multimodal treatment for certain cancers[4-6]. Although the rapid technological advances continue to sustain the field of cancer gene therapy, few individual patients have benefited from the revolution so far. The plethora of clinical trials described confirms that each malignancy has its own ideal strategy based on the associated molecular defects, and there has been rapid progress in this viewpoint. At the same time, there has been a renewed appreciation for the limitations to gene therapy, which include low efficiency of gene transfer, poor specificity of response and methods to accurately evaluate responses, and lack of truly tumor-specific targets at which to aim. With all new therapies, we are climbing a steep learning curve in encountering treatment-related toxicities, as well as profound ethical and regulatory issues[5-9].