乳がん治療薬フルベストラントはオキサリプラチン誘発末梢神経障害を抑制する

<p>The anti-cancer drug oxaliplatin 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, preventive strategies against its side effects have not been established. We screened several sets of small-molecule chemical libraries (more than 3,000 compounds in total) using a newly established <i>in vitro </i>high-throughput phenotypic assay, and 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, using a rat model of oxaliplatin neuropathy, we demonstrated the <i>in vivo </i>efficacy of fulvestrant to prevent oxaliplatin-induced axonal degeneration of the sciatic nerve and mechanical allodynia in histological and behavioural analyses. Thus, our findings reveal a previously unrecognised pharmacological effect of fulvestrant to prevent oxaliplatin-induced painful peripheral neuropathy and may represent a novel prophylactic option for patients receiving oxaliplatin chemotherapy.</p>