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. Issue 1 (12th September 2017)

• Record Type: Journal Article
• Authors: Miyake, Kentaro; Murakami, Takashi; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Li, Yunfeng; Singh, Arun S.; Dry, Sarah M.; Eckardt, Mark A.; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Endo, Itaru; Eilber, Fritz C.; Hoffman, Robert M.
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 1(2018)
• Page Start: 967
• Page End: 972
• Publication Date: 2017-09-12
• Subjects: eribulin -- Ewing's sarcoma -- PDOX -- tumor regression; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26263
• Languages: English
• ISSNs: 0730-2312

Abstract

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 mm 3 : 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. Abstract : Eribulin causes tumor necrosis in a doxorubicin‐resistant Ewing's sarcoma PDOX with a FUS‐ERG fusion and CDKN2A‐deletion. Histological findings. (A) H&E staining of the untreated PDOX tumor. (B) H&E staining of the DOX‐treated PDOX tumor. (C) H&E staining of the Eribulin‐treated PDOX tumor. Necrosis is indicated with white arrows.