| Gastric cancer is one of the most common malignant diseases with highmortality. Although the cure rate has increased recently, the 5- year survival rate of gastric cancer is still 20%~30% in China. With the great development of molecular biology, gene therapy for cancer is from bench to bed. However, little advancement has been achieved in clinical research. The main reason is that the transmissions of traditional gene therapy utilize non-replicative virus or physicochemical methods. Low gene transfer and expression capacity, along with the characteristic of non-target to tumor cells, are the obstacles that hinder the progress of these methods. Tumor-specific replicative viruses overcome these disadvantages. Specifically replicative viruses have evolved to infect tumor cells, replicate, induce cell death and release of viral particles. And these progeny viruses released by virus-mediated lytic infected cells continue to infect surrounding tumor cells, finally spread in tumor tissues. Replication in tumor tissues leads to amplification of the input dose at the tumor site, while a lack of replication in normal tissues can result in efficient clearance and reduced toxicity. In addition to direct lysing tumor cells at the conclusion of the replicative cycle, virus can kill tumor cells by a number of unique mechanisms that distinct from chemotherapeutics or radiotherapy. Therefore, in theory, virotherapy has no toxicity, no dose-limit or no cross-resistance with currently available treatment. Among these viruses, the most attractive one is ONYX-015 (dl!520), an adenovirus with deletion of Elb-55kDa gene encoding P53-binding selected for tumors that already had been inhibited or lost p53 function. The preclinical data reported with this agent were inspiring, it may be the most effective biological therapy up to now. But recent results about curative effect frommultiple clinical trials are not very ideal when ONYX-015 administered singly and the fulfillment of its therapeutic effect must be in virtue of the chemical drugs. We hypothesize that gene therapy utilizing replication-selective oncolytic adenoviruses as vectors, extension of virus-mediated gene delivery, will offer several potential advantages. The therapeutic gene inserted into the genome of the virus will specifically and highly express in the tumor cells with the viruses selectively proliferating in the tumor cells. The new approach, defined as gene-viral therapeutics, can exploit the virtues of gene therapy in coordination with virotherapy and overcome the disadvantages of traditional gene therapy.Several mechanistic approaches for targeting have been reported, and one of them is engineering tumor/tissue-specific promoter into viruses to limit expression of gene(s) necessary for replication in cancer cells. It is reported that telomerase is the most extensive tumor molecular marker to date and accounts for the ability of cancer cells to proliferate in a manner that is out of control. According to the documents, telomerase is highly active in more than 85% of human cancers and activity was detected in 85%~~92% of gastric cancers, but inactive in most somatic cells. hTERT is an essential catalytic subunit of telomerase and has been found to be expressed at high levels in primary tumors and cancer cell lines but repressed in most somatic cells. Recent data suggest that hTERT is a key determinant of the telomerase activity and highly correlated with teloraerase activity. Because the expression of hTERT gene is regulated at the transcription level, we hypothesized that the hTERT promoter may be used for tumor-specific expression of gene necessary for viral replication in cancer cells.Besides the characteristic of unlimited proliferation, another outstanding characteristic of the growing solid tumor is vascularisation. For many years, neoplasms have been found to be able to elicit the production of new capillary endothelium from the host. Now, the progress is definedas tumor angiogenesis, which is crucial component in tumor grow...
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