Combination of the tumor angiogenesis inhibitor bevacizumab and intratumoral oncolytic herpes virus injections as a treatment strategy for human gastric cancers

Tomohiro Deguchi, Toshio Shikano, Hideki Kasuya, Akihiro Nawa, Sawako Fujiwara, Shin Takeda, Tan Gewen, Tevfik T Sahin, Suguru Yamada, Akiyuki Kanzaki, Kazuo Yamamura, Tsutomu Fujii, Hiroyuki Sugimoto, Shuji Nomoto, Saori Fukuda, Yoko Nishikawa, Yasuhiro Kodera, Akimasa Nakao
Hepato-gastroenterology 2012, 59 (118): 1844-50

BACKGROUND/AIMS: Advanced gastric cancer is difficult to treat due to the frequency of liver metastases and peritoneal dissemination. A combination of two new strategies, including the anti-angiogenesis inhibitor bevacizumab and an oncolytic herpes virus is a promising treatment for advanced cancer.

METHODOLOGY: The effects of bevacizumab on oncolytic herpes virus replication and viral cytotoxicity were examined at varying bevacizumab concentrations and viral titers. In addition, the ability of these two new promising anticancer agents to inhibit tumor growth was studied. Histological examinations of CD31 and LacZ were used to assess angiogenesis and virus distribution within the tumor, respectively.

RESULTS: Bevacizumab did not affect viral replication or viral cytotoxicity in vitro. The combination of bevacizumab and the oncolytic herpes virus hrR3 significantly reduced tumor growth in vivo in an experimental gastric cancer model. Bevacizumab inhibited angiogenesis caused by local injection of hrR3 and induced virus spread. Bevacizumab increased the distribution of the intratumorally injected oncolytic herpes virus within the tumor.

CONCLUSIONS: Combination therapy consisting of bevacizumab and an oncolytic herpes virus is a promising new treatment strategy for gastric cancer.

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