A triple-negative matrix-producing breast carcinoma Patient-derived Orthotopic Xenograft (PDOX) mouse model is sensitive to bevacizumab and vinorelbine, regressed by eribulin and resistant to olaparib

Jun Yamamoto, Takuya Murata, Yoshihiko Tashiro, Takashi Higuchi, Norihiko Sugisawa, Hiroto Nishino, Sachiko Inubushi, Yu Sun, Hyein Lim, Kentaro Miyake, Atsushi Hongo, Tsunehisa Nomura, Wataru Saitoh, Takuya Moriya, Hirokazu Tanino, Chihiro Hozumi, Michael Bouvet, Shree Ram Singh, Itaru Endo, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background/Aim: Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triplenegative breast cancer (TNBC). In this study, we determined drug sensitivity for a triple-negative MPBC, without BRCA mutations, in a patient-derived orthotopic xenograft (PDOX) model. Materials and Methods: The MPBC PDOX model was established in the left 2nd mammary gland of nude mouse by implantation of the patient tumor using surgical orthotopic implantation (SOI). We randomized MPBC PDOX mice into 5 groups (n=5 mice/per treatment group) when the tumor volume reached 80 mm3: G1, control-no treatment; G2, bevacizumab [intra-peritoneal (i.p.), weekly, for 2 weeks]; G3, vinorelbine (i.p., weekly, for 2 weeks); G4, olaparib (oral., daily, for 2 weeks); G5, eribulin [intravenous (i.v.), weekly, for 2 weeks]. The mice in each treatment group were sacrificed on day 15. Tumor volume and body weight were measured once/week. Results: The MPBC PDOX model was resistant to olaparib (p=0.22). The MPBC PDOX model treated with bevacizumab and vinorelbine showed significantly suppressed tumor growth compared to the untreated group (p=0.005 and 0.002, respectively). However, only eribulin regressed the tumor (p=0.0001). Eribulin was more effective than olaparib (p=0.0001), bevacizumab (p=0.0025) and vinorelbine (p=0.0061). Conclusion: Eribulin has clinical potential as treatment for triple-negative MPBC patients that are resistant to a PARP inhibitor such as olaparib.

Original languageEnglish
Pages (from-to)2509-2514
Number of pages6
JournalAnticancer research
Volume40
Issue number5
DOIs
Publication statusPublished - 2020 May
Externally publishedYes

Keywords

  • Eribulin
  • Matrix-producing breast carcinoma
  • Nude mice
  • Olaparib
  • PDOX
  • Patient-derived orthotopic xenograft
  • Regression
  • Resistance
  • TNBC
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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