Eribulin regresses a doxorubicin‐resistant Ewing's sarcoma with a FUS‐ERG fusion and CDKN2A‐deletion in a patient‐derived orthotopic xenograft (PDOX) nude mouse model |
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| Authors: | Kentaro Miyake Takashi Murakami Tasuku Kiyuna Kentaro Igarashi Kei Kawaguchi Yunfeng Li Arun S. Singh Sarah M. Dry Mark A. Eckardt Yukihiko Hiroshima Masashi Momiyama Ryusei Matsuyama Takashi Chishima Itaru Endo Fritz C. Eilber Robert M. Hoffman |
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| Affiliation: | 1. AntiCancer Inc., San Diego, California;2. Department of Surgery, University of California, San Diego, California;3. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan;4. Department of Pathology, University of California, Los Angeles, California;5. Division of Hematology‐Oncology, University of California, Los Angeles, California;6. Department of Surgery, Yale School of Medicine, New Haven, Connecticut;7. Division of Surgical Oncology, University of California, Los Angeles, California |
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| Abstract: | Ewing's sarcoma is a recalcitrant tumor greatly in need of more effective therapy. The aim of this study was to determine the efficacy of eribulin on a doxorubicin (DOX)‐resistant Ewing's sarcoma patient derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma PDOX model was previously established in the right chest wall of nude mice from tumor resected form the patient's right chest wall. In the previous study, the Ewing's sarcoma PDOX was resistant to doxorubicin (DOX) and sensitive to palbociclib and linsitinib. In the present study, the PDOX models were randomized into three groups when the tumor volume reached 60 mm3: G1, untreated control (n = 6); G2, DOX treated (n = 6), intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, Eribulin treated (n = 6, intravenous (i.v.) injection, weekly for 2 weeks). All mice were sacrificed on day 15. Changes in body weight and tumor volume were assessed two times per week. Tumor weight was measured after sacrifice. DOX did not suppress tumor growth compared to the control group (P = 0.589), consistent with the previous results in the patient and PDOX. Eribulin regressed tumor size significantly compared to G1 and G2 (P = 0.006, P = 0.017) respectively. No significant difference was observed in body weight among any group. Our results demonstrate that eribulin is a promising novel therapeutic agent for Ewing's sarcoma. |
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| Keywords: | eribulin Ewing's sarcoma PDOX tumor regression |
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