Recently, stage-oriented surgery has been performed for
gastric cancer, but a new strategy is necessary for stage IV
gastric cancer. The first target of gene therapy for
gastric cancer was for stage IV patients with-widespread
lymph node metastases and/or peritoneal dissemination. We reported on suicide gene therapy in experimental
gastric cancer induced by
ENNG in the dog, and the results showed that in situ gene transfer of a suicide gene (Ad. CAGHSV-TK) followed by
prodrug (GCV) treatment may be applicable not only to the primary gastric
tumor, but also to
lymph node metastasis. Next, we assessed the efficacy of in situ gene therapy with Ad. CAGHSV-TK/GCV in
gastric cancer induced by
MNNG in rats, and followed the histopathological changes in the
gastric cancer and HSV-TK gene in peripheral blood for 30 days. The results showed that: 1) apoptosis preceded tissue degeneration; 2) histopathological efficacy requires 30 days after suicide gene therapy; and 3) the HSV-TK gene persisted for 30 days. Based on these studies, we speculated that combination treatment with endoscopy is possible for all early
gastric cancer, i.e., endoscopic mucosal resection of the primary
tumor plus suicide gene therapy for sentinel lymph node
metastasis. New possible strategies for peritoneal dissemination are: 1)
tumor dormancy
therapy with adeno-associated virus (AAV); and 2) combination gene therapy with suicide genes plus gene transfer to provide
immunotherapy.