Gene therapy and virotherapy of gastric cancer: preclinical results and clinical developments

Despite advances in current treatment modalities, the clinical outcome of gastric cancer remains dismal. New treatment modalities are urgently required to improve the prognosis of patients with gastric cancer. Cancer gene therapy and virotherapy comprise a potential category of new therapeutics and will be discussed in this review. To date, various gene therapy strategies have been developed, but first clinical trials reported only limited therapeutic efficacy as a result of limited gene transfer efficiency. Consequently, targeted viral vectors for enhanced delivery of transgenes to tumor cells and replicative viral systems designed to replicate selectively in malignant tissue were developed. Replication-selective oncolytic viral vectors have the advantage over non-replicative systems to cause pronounced bystander effect via self-perpetuating infection of adjacent cells after cytolysis of primary targeted cells. So far, clinical studies on virotherapy showed encouraging results; especially promising are combinations of virotherapy with current modes of treatment like chemo- and radiotherapy, or insertion of therapeutic genes in the viral genome such as combination with enzyme-prodrug therapy. Further research aiming to enhance anti-tumor efficacy and to improve selectivity of infection and replication, will eventually lead to full realization of the therapeutic potential of (replicating) viral vector systems for gastric cancer.