Fulvestrant is a selective estrogen receptor (ER) antagonist. It binds, blocks and degrades estrogen receptor, then inhibits estrogen receptor(ER)-mediated transcriptional activity with an IC50 of 9.4 nM [1-3].
Fulvestrant(3 μM ;1 month) increases the sensitivity of H1975 NSCLC cells to gefitinib[4].Fulvestrant(1-10 µM;72 h) strongly sensitized doxorubicin-induced cytotoxicity in MDR cell lines[5].
Fulvestrant(5 mg/mouse; s.c.; twice per week) significantly inhibited macrophage and neutrophil infiltration in mice cancer model. Fulvestrant decreases ER+ breast cancer growth in the presence of physiologic levels of estradiol in human breast cancer in nude mice[6]. Fulvestrant (5mg/mouse; twice weekly; s.c.) in combination with tamoxifen enhanced tumor regression[7].
References:
[1]. Vergote I, Robertson JF. Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials. Br J Cancer. 2004 Mar;90 Suppl 1(Suppl 1):S11-4. doi: 10.1038/sj.bjc.6601631. PMID: 15094759; PMCID: PMC2750769.
[2]. Osborne CK, Wakeling A, et,al. Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action. Br J Cancer. 2004 Mar;90 Suppl 1(Suppl 1):S2-6. doi: 10.1038/sj.bjc.6601629. PMID: 15094757; PMCID: PMC2750773.
[3]. Dowsett M, Nicholson RI, et,al. Biological characteristics of the pure antiestrogen fulvestrant: overcoming endocrine resistance. Breast Cancer Res Treat. 2005;93 Suppl 1:S11-8. doi: 10.1007/s10549-005-9037-3. PMID: 16247595.
[4]. Shen H, Liu J, et,al. Fulvestrant increases gefitinib sensitivity in non-small cell lung cancer cells by upregulating let-7c expression. Biomed Pharmacother. 2014 Apr;68(3):307-13. doi: 10.1016/j.biopha.2013.10.007. Epub 2013 Nov 7. PMID: 24268810.
[5]. Huang Y, Jiang D, et,al. Fulvestrant reverses doxorubicin resistance in multidrug-resistant breast cell lines independent of estrogen receptor expression. Oncol Rep. 2017 Feb;37(2):705-712. doi: 10.3892/or.2016.5315. Epub 2016 Dec 14. PMID: 28000875; PMCID: PMC5355712.
[6]. Abrahamsson A, Rodriguez GV, et,al. Fulvestrant-Mediated Attenuation of the Innate Immune Response Decreases ER+ Breast Cancer Growth In Vivo More Effectively than Tamoxifen. Cancer Res. 2020 Oct 15;80(20):4487-4499. doi: 10.1158/0008-5472.CAN-20-1705. Epub 2020 Aug 27. PMID: 32855207.
[7]. Mishra AK, Abrahamsson A, et,al. Fulvestrant inhibits growth of triple negative breast cancer and synergizes with tamoxifen in ERα positive breast cancer by up-regulation of ERβ. Oncotarget. 2016 Aug 30;7(35):56876-56888. doi: 10.18632/oncotarget.10871. PMID: 27486755; PMCID: PMC5302959.
Fulvestrant是一种选择性雌激素受体(ER)拮抗剂。它结合、阻断和降解estrogen receptor(ER)，然后抑制estrogen receptor(ER)介导的转录活性，IC50为9.4 nM[1-3]。
Fulvestrant (3 μM ;1 month)增加H1975 NSCLC细胞对吉非替尼的敏感性[4]。Fulvestrant (1-10 µM;72 h)对多耐药细胞系中阿霉素诱导的细胞毒性具有强致敏作用[5]。Fulvestrant (5 mg/mouse; s.c.; twice per week) 显著抑制小鼠肿瘤模型中巨噬细胞和中性粒细胞的浸润。在裸鼠人乳腺癌中，在存在生理水平雌二醇的情况下，Fulvestrant可降低ER+乳腺癌的生长[6]。Fulvestrant (5mg/mouse; twice weekly; s.c.)联合tamoxifen可促进肿瘤消退[7]。