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

Author:

Kiyuna, Tasuku

Tome, Yasunori

Miyake, Kentaro

Murakami, Takashi

Oshiro, Hiromichi

Igarashi, Kentaro

Kawaguchi, Kei

Hsu, John

Singh, Manish

Li, Yunfeng

Nelson, Scott

Bouvet, Michael

Singh,Shree Ram

Kanaya, Fuminori

Hoffman, Robert M
Author Address

AntiCancer Inc., San Diego, CA, U.S.A., Department of Surgery, University of California, San Diego, CA, U.S.A., Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan., Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan all@anticancer.com yash_toume@hotmail.com singhshr@mail.nih.gov., Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, U.S.A., Department of Pathology, University of California, Los Angeles, CA, U.S.A., Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A. all@anticancer.com yash_toume@hotmail.com singhshr@mail.nih.gov., AntiCancer Inc., San Diego, CA, U.S.A. all@anticancer.com yash_toume@hotmail.com singhshr@mail.nih.gov.,

Abstract:

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%. 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. The osteosarcoma PDOX was resistant to doxorubicin, sunitinib, and pazopanib. In contrast, eribulin and temozolomide arrested tumor growth. 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. Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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