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

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.

authors

Igarashi K,Kawaguchi K,Kiyuna T,Miyake K,Higuchi T,Yamamoto N,Hayashi K,Kimura H,Miwa S,Singh SR,Tsuchiya H,Hoffman RM

doi

10.21873/cgp.20194

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

351-358

issue

4

eissn

1109-6535

issn

1790-6245

pii

17/4/351

journal_volume

17

pub_type

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