[Possibility and future problems of gene therapy for gastric cancer].
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.
Matsukura
N
N
First Department of Surgery, Nippon Medical School, Tokyo, Japan.
Onda
M
M
Shimada
T
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005544:Forecasting; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000639:trends*; D005822:Genetic Vectors; D006801:Humans; D008207:Lymphatic Metastasis; D051381:Rats; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*