Higuchi Takashi, Sugisawa Norihiko, Miyake Kentaro, Oshiro Hiromichi, Yamamoto Norio, Hayashi Katsuhiro, Kimura Hiroaki, Miwa Shinji, Igarashi Kentaro, Bouvet Michael, Singh Shree Ram, Tsuchiya Hiroyuki, Hoffman Robert M
AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan.
AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
Transl Oncol. 2019 Sep;12(9):1257-1263. doi: 10.1016/j.tranon.2019.06.002. Epub 2019 Jul 9.
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.
化疗耐药性骨肉瘤是一种难治性疾病。它是导致通常为青少年或年轻成年人患者死亡的常见原因。本研究的目的是在患者来源的原位异种移植（PDOX）模型中，确定olaratumab（OLA）、多柔比星（DOX）和顺铂（CDDP）联合用药对一线治疗耐药的骨肉瘤的疗效。骨肉瘤PDOX模型被随机分为六个治疗组，每组六只小鼠：对照组；单独使用CDDP组；DOX和CDDP组；OLA + DOX组；OLA + CDDP组；以及OLA + DOX和CDDP组。在治疗的14天内测量肿瘤大小和体重。仅OLA + DOX和CDDP联合治疗使肿瘤生长出现消退。用这种三联药物组合治疗的肿瘤坏死最多，Ki-67指数最低。本研究证明了PDOX模型在识别化疗耐药性骨肉瘤新的有效治疗策略方面的作用。
