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

Kentaro Miyake, Tasuku Kiyuna, Kei Kawaguchi, Takashi Higuchi, Hiromichi Oshiro, Zhiying Zhang, Sintawat Wangsiricharoen, Sahar Razmjooei, Yunfeng Li, Scott D. Nelson, Takashi Murakami, Yukihiko Hiroshima, Ryusei Matsuyama, Michael Bouvet, Sant P. Chawla, Shree Ram Singh, Itaru Endo, Robert M. Hoffman

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: 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. Methods: 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 mm 3 : 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. Results: 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). Conclusions: Our findings suggest that REG has clinical potential for ES patients whose tumors respond to REG in a PDOX model.

Original languageEnglish
Pages (from-to)809-815
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume83
Issue number5
DOIs
Publication statusPublished - 2019 May 1
Externally publishedYes

Keywords

  • Ewing’s sarcoma
  • Nude mouse
  • Patient-derived orthotopic xenograft
  • PDOX
  • Regorafenib

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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  • Cite this

    Miyake, K., Kiyuna, T., Kawaguchi, K., Higuchi, T., Oshiro, H., Zhang, Z., Wangsiricharoen, S., Razmjooei, S., Li, Y., Nelson, S. D., Murakami, T., Hiroshima, Y., Matsuyama, R., Bouvet, M., Chawla, S. P., Singh, S. R., Endo, I., & Hoffman, R. M. (2019). Regorafenib regressed a doxorubicin-resistant Ewing’s sarcoma in a patient-derived orthotopic xenograft (PDOX) nude mouse model. Cancer Chemotherapy and Pharmacology, 83(5), 809-815. https://doi.org/10.1007/s00280-019-03782-w