Eribulin Suppressed Cisplatinum- And Doxorubicin-resistant Recurrent Lung Metastatic Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model

Tasuku Kiyuna, Yasunori Tome, Kentaro Miyake, Takashi Murakami, Hiromichi Oshiro, Kentaro Igarashi, Kei Kawaguchi, John Hsu, Manish Singh, Yunfeng Li, Scott Nelson, Michael Bouvet, Shree Ram Singh, Fuminori Kanaya, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Background: Osteosarcoma is a recalcitrant disease treated with surgery and intensive chemotherapy as standard. The 5-year survival rate of patients with relapsed and lung metastatic osteosarcoma is as low as 20%. Materials and Methods: A 16-year-old patient developed left distal femoral high-grade osteosarcoma and underwent cisplatinum-based neoadjuvant chemotherapy and surgery. From the resected tumor, a patient-derived orthotopic xenograft (PDOX) model was established in the femur of nude mice. PDOX models were randomized into the following groups: untreated control, or treatment with doxorubicin (3 mg/kg, i.p., weekly for 14 days), sunitinib (40 mg/kg, oral gavage, daily for 14 days), pazopanib (100 mg/kg, oral gavage, daily for 14 days), temozolomide(25 mg/kg, oral gavage, daily for 14 days), and eribulin (1.5 mg/kg, i.p., daily for 14 days). Tumor volume and body weight were monitored twice a week. Results: The osteosarcoma PDOX was resistant to doxorubicin, sunitinib, and pazopanib. In contrast, eribulin and temozolomide arrested tumor growth. Conclusion: This study demonstrated the utility of the PDOX model in allowing effective from non-effective drugs to be distinguished in a model in which the tumor was growing on the organ corresponding to that of the patient.

Original languageEnglish
Pages (from-to)4775-4779
Number of pages5
JournalAnticancer research
Volume39
Issue number9
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • Doxorubicin
  • Eribulin
  • Metastasis
  • Osteosarcoma
  • PDOX
  • Patient-derived orthotopic xenograft
  • Pazopanib
  • Precision medicine
  • Sunitinib
  • Temozolomide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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