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

被引：22

作者：

Higuchi, Takashi ^{[1
,2
,3
]}

Sugisawa, Norihiko ^{[1
,2
]}

Miyake, Kentaro ^{[1
,2
]}

Oshiro, Hiromichi ^{[1
,2
]}

Yamamoto, Norio ^{[3
]}

Hayashi, Katsuhiro ^{[3
]}

Kimura, Hiroaki ^{[3
]}

Miwa, Shinji ^{[3
]}

Igarashi, Kentaro ^{[3
]}

Bouvet, Michael ^{[2
]}

Singh, Shree Ram ^{[4
]}

Tsuchiya, Hiroyuki ^{[3
]}

Hoffman, Robert M. ^{[1
,2
]}

机构：

[1] AntiCancer Inc, San Diego, CA 92111 USA

[2] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA

[3] Kanazawa Univ, Dept Orthoped Surg, Kanazawa, Ishikawa, Japan

[4] NCI, Basic Res Lab, Frederick, MD 21701 USA

来源：

TRANSLATIONAL ONCOLOGY | 2019年 / 12卷 / 09期

基金：

日本学术振兴会;

关键词：

GROWTH-FACTOR RECEPTOR; SOFT-TISSUE SARCOMA; MONOCLONAL-ANTIBODY; PDGFR-ALPHA; PHASE-I; INHIBITION; BONE;

D O I：

10.1016/j.tranon.2019.06.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1257 / 1263

页数：7

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