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

• DOI: 10.18632/oncotarget.14040
• Publication Date: 2016-12-22T16:29:38Z
• Authors: 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; Robert M. Hoffman
• Keywords: Male; Niacinamide; Salmonella typhimurium; patient-derived xenograft; Time Factors; Adolescent; Pediatric Cancer; Nude; Oncology and Carcinogenesis; Drug Resistance; tumor-targeting; 610; Mice, Nude; Antineoplastic Agents; Bone Neoplasms; Salmonella typhimurium A1-R; Mice; Necrosis; 03 medical and health sciences; Rare Diseases; 0302 clinical medicine; Clinical Research; osteosarcoma; Animals; Humans; Molecular Targeted Therapy; Protein Kinase Inhibitors; Cancer; Pediatric; Osteosarcoma; Phenylurea Compounds; Sorafenib; Xenograft Model Antitumor Assays; Tumor Burden; 3. Good health; Biological Therapy; Orphan Drug; Emerging Infectious Diseases; Drug Resistance, Neoplasm; Neoplasm; nude mouse; Research Paper

// Takashi Murakami 1, 2, 3 , Kentaro Igarashi 1 Kei Kawaguchi Tasuku Kiyuna Yong Zhang Ming Zhao Yukihiko Hiroshima Scott D. Nelson 5 Sarah M. Dry Yunfeng Li Jane Yanagawa 6 Tara Russell Noah Federman 7 Arun Singh 4 Irmina Elliott Ryusei Matsuyama Chishima Kuniya Tanaka Itaru Endo Fritz C. Eilber Robert Hoffman 2 AntiCancer, Inc., San Diego, California, USA Department of Surgery, University Gastroenterological Graduate School Medicine, Yokohama City University, Yokohama, Japan Division Hematology-Oncology, Los Angeles, Pathology, California Surgical Oncology, Pediatrics and Orthopaedics, David Geffen Mattel Children’s Hospital, UCLA’s Jonsson Comprehensive Cancer Center, Correspondence to: Hoffman, email: [e-mail] Eilber, [e-mail] Keywords: osteosarcoma, nude mouse, patient-derived xenograft, Salmonella typhimurium A1-R, tumor-targeting Received: October 20, 2016      Accepted: November 16, Published: December 2016 ABSTRACT Osteosarcoma occurs mostly in children young adults, who are treated with multiple agents combination limb-salvage surgery. However, the overall 5-year survival rate for patients recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory would benefit from precise individualized therapy. We report here that a growing subcutaneous nude-mouse model was regressed by A1-R ( S. p<0.001 compared to untreated control). The only partially sensitive molecular-targeting drug sorafenib, did arrest its growth. more effective than sorafenib (P <0.001). grew tumors caused extensive necrosis tumor tissue. These data show powerful therapy an xenograft model.