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

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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10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)967-972
Number of pages6
JournalJournal of Cellular Biochemistry
Volume119
Issue number1
DOIs
Publication statusPublished - 2018 Jan
Externally publishedYes

Keywords

  • eribulin
  • Ewing's sarcoma
  • PDOX
  • tumor regression

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Miyake, K., Murakami, T., Kiyuna, T., Igarashi, K., Kawaguchi, K., Li, Y., Singh, A. S., Dry, S. M., Eckardt, M. A., Hiroshima, Y., Momiyama, M., Matsuyama, R., Chishima, T., Endo, I., Eilber, F. C., & Hoffman, R. M. (2018). 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. Journal of Cellular Biochemistry, 119(1), 967-972. https://doi.org/10.1002/jcb.26263