Takuya Moriya
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Pathology,
   Position   Professor
Article types 原著
Language English
Peer review Peer reviewed
Title 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.
Journal Formal name:Anticancer research
Abbreviation:Anticancer Res
ISSN code:17917530/02507005
Domestic / ForeginForegin
Volume, Issue, Page 40(5),pp.2509-2514
Author and coauthor Yamamoto Jun, Murata Takuya, Tashiro Yoshihiko, Higuchi Takashi, Sugisawa Norihiko, Nishino Hiroto, Inubushi Sachiko, Sun Y U, Lim Hyein, Miyake Kentaro, Hongo Atsushi, Nomura Tsunehisa, Saitoh Wataru, Moriya Takuya, Tanino Hirokazu, Hozumi Chihiro, Bouvet Michael, Singh Shree Ram, Endo Itaru, Hoffman Robert M
Publication date 2020/05
Summary BACKGROUND/AIM:Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triple-negative 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.
DOI 10.21873/anticanres.14221
PMID 32366395