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

Abstract

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.

• Authors: 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
• Journal: Translational oncology (Transl Oncol) Vol. 12 Issue 9 Pg. 1257-1263 (Sep 2019) ISSN: 1936-5233 [Print] United States
• PMID: 31299622 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.