Eribulin Regresses a Doxorubicin-resistant Dedifferentiated Liposarcoma in a Patient-derived Orthotopic Xenograft Mouse Model

Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Takashi Higuchi, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalArticle

Abstract

BACKGROUND/AIM: Dedifferentiated liposarcoma (DDLPS) is recalcitrant type of sarcoma. DDLPS has a low survival rate with high recurrence and metastasis. In the present study, we evaluated the efficacy of several drugs against doxorubicin-resistant DDLPS in a patient-derived orthotopic xenograft (PDOX) model for precision oncology. To establish the PDOX model, a tumor from a patient who had recurrent high-grade DDLPS from the retroperitoneum was previously grown orthotopically in the retroperitoneum of nude mice. MATERIALS AND METHODS: We randomized DDLPS PDOX models into 8 treatment groups when tumor volume became approximately 100 mm3: control, no treatment; G2, doxorubicin (DOX); G3, pazopanib (PAZ); G4, gemcitabine (GEM) combined with docetaxel (DOC); G5, trabectedin (YON); G6, temozolomide (TEM); G7, palbociclib (PAL); G8, eribulin (ERB). Tumor length and width were measured both at the beginning and at the end of treatment. RESULTS: At the end of treatment (day 14), all treatments significantly inhibited DDLPS PDOX tumor growth compared to the untreated control, except DOX. ERB was significantly more effective and regressed tumor volume compared to other treatments on day 14 after initiation of treatment. No significant differences were found in the relative body weight on day 14 compared to day 0 in any group. CONCLUSION: The clinical potential of ERB against DDLPS is herein presented in a PDOX model.

Original languageEnglish
Pages (from-to)351-358
Number of pages8
JournalCancer Genomics and Proteomics
Volume17
Issue number4
DOIs
Publication statusPublished - 2020 Jul 1

Keywords

  • PDOX
  • Patient-derived orthotopic xenograft
  • dedifferentiated liposarcoma
  • doxorubicin resistance
  • eribulin
  • regression

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

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    Igarashi, K., Kawaguchi, K., Kiyuna, T., Miyake, K., Higuchi, T., Yamamoto, N., Hayashi, K., Kimura, H., Miwa, S., Singh, S. R., Tsuchiya, H., & Hoffman, R. M. (2020). Eribulin Regresses a Doxorubicin-resistant Dedifferentiated Liposarcoma in a Patient-derived Orthotopic Xenograft Mouse Model. Cancer Genomics and Proteomics, 17(4), 351-358. https://doi.org/10.21873/cgp.20194