New pharmacological effect of fulvestrant to prevent oxaliplatin-induced neurodegeneration and mechanical allodynia in rats

Shota Yamamoto, Tomohiro Yamashita, Mayu Ito, Jose M.M. Caaveiro, Nobuaki Egashira, Hidetoshi Tozaki-Saitoh, Makoto Tsuda

研究成果: Contribution to journalArticle査読

4 被引用数 (Scopus)

抄録

Oxaliplatin, which is widely used as chemotherapy for certain solid cancers, frequently causes peripheral neuropathy. Commonly described neuropathic symptoms include aberrant sensations such as mechanical allodynia (hypersensitivity to normally innocuous stimuli). Although oxaliplatin neuropathy is a dose-limiting toxicity, there are no established preventive strategies available at present. By screening several sets of small-molecule chemical libraries (more than 3,000 compounds in total) using a newly established in vitro high-throughput phenotypic assay, we identified fulvestrant, a clinically approved drug for the treatment of breast cancer in postmenopausal women, as having a protective effect on oxaliplatin-induced neuronal damage. Furthermore, histological and behavioural analyses using a rat model of oxaliplatin neuropathy demonstrated the in vivo efficacy of fulvestrant to prevent oxaliplatin-induced axonal degeneration of the sciatic nerve and mechanical allodynia. Furthermore, fulvestrant did not interfere with oxaliplatin-induced cytotoxicity against cancer cells. Thus, our findings reveal a previously unrecognised pharmacological effect of fulvestrant to prevent oxaliplatin-induced painful peripheral neuropathy without impairing its cytotoxicity against cancer cells and may represent a novel prophylactic option for patients receiving oxaliplatin chemotherapy.

本文言語英語
ページ(範囲)2107-2113
ページ数7
ジャーナルInternational Journal of Cancer
145
8
DOI
出版ステータス出版済み - 10 15 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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