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

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.

• Authors: 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
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 9 Pg. 4775-4779 (Sep 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 31519578 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Furans
• Ketones
• Doxorubicin
• eribulin
• Cisplatin

Topics

• Adolescent
• Animals
• Cisplatin (pharmacology)
• Disease Models, Animal
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Furans (pharmacology)
• Humans
• Ketones (pharmacology)
• Lung Neoplasms (drug therapy, pathology, secondary)
• Mice
• Osteosarcoma (drug therapy, pathology)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays