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Research ArticleExperimental Studies

Antitumor Activity of Eribulin After Fulvestrant Plus CDK4/6 Inhibitor in Breast Cancer Patient-derived Xenograft Models

YUKI NIWA, MAKOTO ASANO, TAKAYUKI NAKAGAWA, DAMIEN FRANCE, TARO SEMBA and YASUHIRO FUNAHASHI
Anticancer Research December 2020, 40 (12) 6699-6712; DOI: https://doi.org/10.21873/anticanres.14693
YUKI NIWA
1Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan;
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MAKOTO ASANO
1Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan;
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TAKAYUKI NAKAGAWA
1Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan;
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DAMIEN FRANCE
2Oncodesign, Dijon, France
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TARO SEMBA
1Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan;
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YASUHIRO FUNAHASHI
1Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan;
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  • For correspondence: y-funahashi@hhc.eisai.co.jp
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Abstract

Background/Aim: There is no established standard chemotherapy after administration of the combination endocrine plus CDK4/6 inhibitor therapy for luminal-type breast cancer. We used patient-derived xenograft (PDX) models to determine the antitumor activity of eribulin and capecitabine after endocrine therapy plus CDK4/6 inhibitor. Materials and Methods: We examined the antitumor activity of fulvestrant, palbociclib, eribulin, and capecitabine in 4 luminal-type breast cancer PDX models (OD-BRE-0188, -0438, -0450, -0745). In OD-BRE-0438, we determined the antitumor activity of chemotherapy after fulvestrant–palbociclib treatment. We also performed immunohistochemical analysis to explore the effects of treatment on E-cadherin in tumor tissues. Results: Fulvestrant, fulvestrant-palbociclib and chemotherapy had antitumor activity in the 4 PDX models. In OD-BRE-0438 (the most resistant to fulvestrant–palbociclib), eribulin had superior antitumor activity to capecitabine after fulvestrant plus palbociclib. Only eribulin tended to increase E-cadherin expression. Conclusion: Eribulin had superior antitumor activity to capecitabine after fulvestrant–palbociclib in the OD-BRE-0438 model.

Key Words:
  • CDK4/6 inhibitor
  • eribulin mesylate
  • luminal-type breast cancer
  • patient-derived xenograft model
  • reversal of epithelial-mesenchymal transition
  • preclinical trial
  • Received October 30, 2020.
  • Revision received November 15, 2020.
  • Accepted November 16, 2020.
  • Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 40 (12)
Anticancer Research
Vol. 40, Issue 12
December 2020
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Antitumor Activity of Eribulin After Fulvestrant Plus CDK4/6 Inhibitor in Breast Cancer Patient-derived Xenograft Models
YUKI NIWA, MAKOTO ASANO, TAKAYUKI NAKAGAWA, DAMIEN FRANCE, TARO SEMBA, YASUHIRO FUNAHASHI
Anticancer Research Dec 2020, 40 (12) 6699-6712; DOI: 10.21873/anticanres.14693

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Antitumor Activity of Eribulin After Fulvestrant Plus CDK4/6 Inhibitor in Breast Cancer Patient-derived Xenograft Models
YUKI NIWA, MAKOTO ASANO, TAKAYUKI NAKAGAWA, DAMIEN FRANCE, TARO SEMBA, YASUHIRO FUNAHASHI
Anticancer Research Dec 2020, 40 (12) 6699-6712; DOI: 10.21873/anticanres.14693
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Keywords

  • CDK4/6 inhibitor
  • eribulin mesylate
  • luminal-type breast cancer
  • patient-derived xenograft model
  • reversal of epithelial-mesenchymal transition
  • preclinical trial
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