Eribulin Inhibits Osteosarcoma in a Clinically-accurate Bone-tumor-insertion PDOX Mouse Model.

Nathaniel F Wu,Jun Yamamoto,Yusuke Aoki,Robert M Hoffman,Michael Bouvet

doi:10.21873/anticanres.14943

Abstract

Osteosarcoma is a rare type of bone cancer that affects mostly children and adolescents. First-line chemotherapy for osteosarcoma has not been improved for many decades. Eribulin has been used to treat breast cancer and liposarcoma in the clinic. A patient-derived orthotopic xenograft (PDOX) mouse model of osteosarcoma was established by tumor insertion within the tibia. This model more closely mimics osteosarcoma in clinical settings and was used to test the efficacy of eribulin. Tibia-insertion osteosarcoma PDOX mouse models were randomized into two groups: a control group (n=4) and an eribulin-treatment group (n=5). Mice were treated for fourteen days, four weeks after initial implantation. Tumor size and body weight were measured, and tumor histology was examined. Significant tumor growth inhibition (p=0.044) was observed in mice treated with eribulin compared to the control group. Histology demonstrated necrosis in the eribulin-treated tumors. There was no body-weight loss in the treated mice. Eribulin may be a clinically-effective, off-label chemotherapy for recalcitrant osteosarcoma that has failed first- and second-line therapy.

Highlights

Our laboratory developed the patient-derived orthotopic xenograft (PDOX) model for many cancer types, including osteosarcoma [5, 10]
We developed an improved osteosarcoma PDOX model in which the tumor is inserted into a hole made in the tibia of nude mice in order for the patient osteosarcoma to grow within the bone, as it does clinically [11]
Eribulin inhibited tumor growth of the osteosarcoma PDOX model: At day 14, the mean relative tumor volume in the control mice was 8.9 mm3 and in the eribulintreated mice, relative tumor volume was 5.4 mm3 (p=0.044) (Figure 3)

Summary

Introduction

Our laboratory developed the patient-derived orthotopic xenograft (PDOX) model for many cancer types, including osteosarcoma [5, 10]. We developed an improved osteosarcoma PDOX model in which the tumor is inserted into a hole made in the tibia of nude mice in order for the patient osteosarcoma to grow within the bone, as it does clinically [11]. Eribulin is a third-line FDA-approved therapy for metastatic breast-cancer patients who were previously treated with an anthracycline and a taxane [12]. Eribulin has been approved for the treatment of metastatic liposarcoma patients who have progressed after anthracycline treatment [12]. The present study uses an orthotopic, more-clinically-accurate osteosarcoma mouse model to test eribulin as a potential effective off-label chemotherapy for treating patients with osteosarcoma, who have failed first-line chemotherapy [11]

Methods

Results

Conclusion