The Combination of Olaratumab with Doxorubicin and Cisplatinum Regresses a Chemotherapy-Resistant Osteosarcoma in a Patient-Derived Orthotopic Xenograft Mouse Model

Takashi Higuchi; Norihiko Sugisawa; Kentaro Miyake; Hiromichi Oshiro; Norio Yamamoto; Katsuhiro Hayashi; Hiroaki Kimura; Shinji Miwa; Kentaro Igarashi; Michael Bouvet; Shree Ram Singh; Hiroyuki Tsuchiya; Robert M. Hoffman

Translational Oncology (Sep 2019)

The Combination of Olaratumab with Doxorubicin and Cisplatinum Regresses a Chemotherapy-Resistant Osteosarcoma in a Patient-Derived Orthotopic Xenograft Mouse Model

Takashi Higuchi,
Norihiko Sugisawa,
Kentaro Miyake,
Hiromichi Oshiro,
Norio Yamamoto,
Katsuhiro Hayashi,
Hiroaki Kimura,
Shinji Miwa,
Kentaro Igarashi,
Michael Bouvet,
Shree Ram Singh,
Hiroyuki Tsuchiya,
Robert M. Hoffman

Affiliations

Takashi Higuchi: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Norihiko Sugisawa: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Kentaro Miyake: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Hiromichi Oshiro: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Norio Yamamoto: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Katsuhiro Hayashi: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Hiroaki Kimura: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Shinji Miwa: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Kentaro Igarashi: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Michael Bouvet: Department of Surgery, University of California, San Diego, CA, USA
Shree Ram Singh: Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA; Corresponding author at: Shree Ram Singh, National Cancer Institute, Frederick, MD, USA.
Hiroyuki Tsuchiya: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan; Corresponding author at: Hiroyuki Tsuchiya, Kanazawa University, Kanazawa, Japan.
Robert M. Hoffman: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Corresponding author at: Robert M Hoffman, AntiCancer, Inc., CA, USA

Journal volume & issue: Vol. 12, no. 9
pp. 1257 – 1263

Abstract

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Chemotherapy-resistant osteosarcoma is a recalcitrant disease. It is a frequent cause of death to the patients who are usually adolescent or young adults. The goal of the present study was to determine the efficacy of the combination of olaratumab (OLA), doxorubicin (DOX), and cisplatinum (CDDP) on osteosarcoma, which is resistant to first-line therapy, in a patient-derived orthotopic xenograft (PDOX) model. The osteosarcoma PDOX model was randomized into six treatment groups of six mice: control; CDDP alone; DOX and CDDP; OLA + DOX; OLA + CDDP; and OLA + DOX and CDDP. Tumor size and body weight were measured during 14 days of treatment. Tumor growth was regressed only by the treatment with a combination of OLA + DOX and CDDP. Tumors treated with this three-drug combination had the most tumor necrosis and the lowest Ki-67 index. The present study demonstrates the power of the PDOX model to identify novel effective treatment strategy for chemotherapy-resistant osteosarcoma.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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