Regorafenib regressed a doxorubicin-resistant Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) nude mouse model

Author:

Miyake, Kentaro

Kiyuna, Tasuku

Kawaguchi, Kei

Higuchi, Takashi

Oshiro, Hiromichi

Zhang, Zhiying

Wangsiricharoen, Sintawat

Razmjooei, Sahar

Li, Yunfeng

Nelson, Scott D

Murakami, Takashi

Hiroshima, Yukihiko

Matsuyama, Ryusei

Bouvet, Michael

Chawla, Sant P

Singh, Shree Ram [ORCID]

Endo, Itaru

Hoffman, Robert M
Author Address

AntiCancer Inc, San Diego, CA, USA., Department of Surgery, University of California, San Diego, CA, USA., Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Department of Pathology, University of California, Los Angeles, CA, USA., Sarcoma Oncology Center, 2811 Wilshire Blvd., Suite 414, 90403, Santa Monica, CA, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. singhshr@mail.nih.gov., Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. endoit@med.yokohama-cu.ac.jp., AntiCancer Inc, San Diego, CA, USA. all@anticancer.com., Department of Surgery, University of California, San Diego, CA, USA. all@anticancer.com.,

Abstract:

Ewing's sarcoma (ES) is a rare and recalcitrant disease which is in need of a development of a novel effective therapy. The aim of this study was to investigate the efficacy of regorafenib on an ES tumor in a patient-derived orthotopic xenograft (PDOX) model. The ES PDOX models were established orthotopically in the right chest wall of nude mice to match the site of the tumor in the donor patient. The ES PDOX models were randomized into three groups (G) when the tumor volume reached 75 mm3: G1: untreated control; G2: doxorubicin (DOX) (i.p., 3 mg/kg, weekly, 2 weeks); G3: regorafenib (REG) (p.o., 30 mg/kg, daily, 2 weeks). Tumor volume and body weight were measured twice a week. All mice were sacrificed on day 15. DOX was ineffective compared to the control group (P?=?0.229). REG regressed the tumor size (P?< ?0.001 and P?< ?0.001, relative to control and DOX, respectively). Our findings suggest that REG has clinical potential for ES patients whose tumors respond to REG in a PDOX model.

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