Abstract 1103: Novel theranostic strategy against scirrhous gastric cancer; combination of chemotherapy and fluorescence oncolytic adenovirus
Authors: Ishikawa Wataru , Kikuchi Satoru , Tazawa Hiroshi , Kuroda Shinji , Noma Kazuhiro , Kishimoto Hiroyuki , Nagasaka Takeshi , Nishizaki Masahiko , Kagawa Shunsuke , Fujiwara Toshiyoshi 
Published: July 2017

Background: Gastric cancer is one of the most common cancers worldwide, especially in Eastern Asia. Scirrhous gastric cancer (SGC), which is characterized by poorly differentiated tumor cells that diffusely infiltrate the gastric wall, accounts for 10% of all gastric cancers, and often causes peritoneal metastasis. Peritoneal carcinomatosis shows the worst prognosis among various metastatic patterns. Since it is difficult to detect peritoneal micrometastasis preoperatively or intraoperatively, SGC patients with peritoneal micrometastasis show the recurrence and refractory to conventional systemic chemotherapy after surgery. In recent year, intraperitoneal (i.p.) administration of paclitaxel (PTX) has been shown to have therapeutic effects against ovarian cancer with peritoneal metastasis. However, the effective treatment option to overcome peritoneal metastasis of SGC has not been developed yet, although i.p. administration of some chemotherapeutic agents has been attempted to SGC. Therefore, a novel therapeutic strategy is required for the treatment of peritoneal metastasis of SGC.

Methods: We previously developed a telomerase-dependent replication-selective adenovirus OBP-401 (TelomeScan), which can replicate within the tumor cells selectively and express green fluorescent protein (GFP). Moreover, OBP-401 infection also induces tumor-specific cell death in monotherapy or combination therapy with chemotherapy. In this study, we assessed synergistic effects in combination with novel theranostic agent OBP-401 and chemotherapeutic agent paclitaxel (PTX) using human SGC cell lines (GCIY and KATO III). In vitro experiment, SGC cells and normal human lung fibroblast (NHLF) cells were infected with OBP-401 at various doses. PTX was administrated after 48 hours of virus infection. Twenty-four hours after PTX administration, we evaluated the anti-tumor effect by XTT assay, and analyzed the synergistic effect by CalcuSyn Software.

Results: SGC cells were visualized as GFP-positive cells selectively by the infection of OBP-401, whereas NHLF cells were not visualized with OBP-401. In both SGC cell lines, the suppression of cell viability dose-dependently by administration of OBP-401 or PTX alone was confirmed. OBP-401 synergistically suppressed the viability of SGC cells in combination with PTX as compared to monotherapy.

Conclusions: These results suggest that OBP-401 has a promising potential to detect peritoneal micrometastasis of SGC intraoperatively and combination of OBP-401 and PTX would be a novel theranostic strategy for the treatment of peritoneal metastasis of SGC.

Citation Format: Wataru Ishikawa, Satoru Kikuchi, Hiroshi Tazawa, Shinji Kuroda, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara. Novel theranostic strategy against scirrhous gastric cancer; combination of chemotherapy and fluorescence oncolytic adenovirus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1103. doi:10.1158/1538-7445.AM2017-1103