Oncotarget

Research Papers:

Tumor-targeting Salmonella typhimurium A1-R regresses an osteosarcoma in a patient-derived xenograft model resistant to a molecular-targeting drug

Takashi Murakami _, Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Yong Zhang, Ming Zhao, Yukihiko Hiroshima, Scott D. Nelson, Sarah M. Dry, Yunfeng Li, Jane Yanagawa, Tara Russell, Noah Federman, Arun Singh, Irmina Elliott, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, Itaru Endo, Fritz C. Eilber and Robert M. Hoffman

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Oncotarget. 2017; 8:8035-8042. https://doi.org/10.18632/oncotarget.14040

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Abstract

Takashi Murakami1,2,3, Kentaro Igarashi1, Kei Kawaguchi1, Tasuku Kiyuna1, Yong Zhang1, Ming Zhao1, Yukihiko Hiroshima3, Scott D. Nelson5, Sarah M. Dry5, Yunfeng Li5, Jane Yanagawa6, Tara Russell6, Noah Federman7, Arun Singh4, Irmina Elliott6, Ryusei Matsuyama3, Takashi Chishima3, Kuniya Tanaka3, Itaru Endo3, Fritz C. Eilber6, Robert M. Hoffman1,2

1AntiCancer, Inc., San Diego, California, USA

2Department of Surgery, University of California, San Diego, California, USA

3Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan

4Division of Hematology-Oncology, University of California, Los Angeles, California, USA

5Department of Pathology, University of California Los Angeles, California, USA

6Division of Surgical Oncology, University of California, Los Angeles, California, USA

7Department of Pediatrics and Department of Orthopaedics, David Geffen School of Medicine, Mattel Children’s Hospital, UCLA’s Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA

Correspondence to:

Robert M. Hoffman, email: [email protected]

Fritz C. Eilber, email: [email protected]

Keywords: osteosarcoma, nude mouse, patient-derived xenograft, Salmonella typhimurium A1-R, tumor-targeting

Received: October 20, 2016     Accepted: November 16, 2016     Published: December 20, 2016

ABSTRACT

Osteosarcoma occurs mostly in children and young adults, who are treated with multiple agents in combination with limb-salvage surgery. However, the overall 5-year survival rate for patients with recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory patients would benefit from precise individualized therapy. We report here that a patient-derived osteosarcoma growing in a subcutaneous nude-mouse model was regressed by tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R, p<0.001 compared to untreated control). The osteosarcoma was only partially sensitive to the molecular-targeting drug sorafenib, which did not arrest its growth. S. typhimurium A1-R was significantly more effective than sorafenib (P <0.001). S. typhimurium grew in the treated tumors and caused extensive necrosis of the tumor tissue. These data show that S. typhimurium A1-R is powerful therapy for an osteosarcoma patient-derived xenograft model.


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