دورية أكاديمية

Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer

التفاصيل البيبلوغرافية
العنوان: Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer
المؤلفون: Swaathi Jayaraman, Xiaonan Hou, Mary J. Kuffel, Vera J. Suman, Tanya L. Hoskin, Kathryn E. Reinicke, David G. Monroe, Krishna R. Kalari, Xiaojia Tang, Megan A. Zeldenrust, Jingfei Cheng, Elizabeth S. Bruinsma, Sarah A. Buhrow, Renee M. McGovern, Stephanie L. Safgren, Chad A. Walden, Jodi M. Carter, Joel M. Reid, James N. Ingle, Matthew M. Ames, John R. Hawse, Matthew P. Goetz
المصدر: Breast Cancer Research, Vol 22, Iss 1, Pp 1-12 (2020)
بيانات النشر: BMC, 2020.
سنة النشر: 2020
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: Z-endoxifen, Tamoxifen, Tumor growth in vivo, Estrogen-regulated genes, AI-resistant and AI-sensitive ER+ breast cancer, Signaling kinase, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Background The tamoxifen metabolite, Z-endoxifen, demonstrated promising antitumor activity in endocrine-resistant estrogen receptor-positive (ER+) breast cancer. We compared the antitumor activity of Z-endoxifen with tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), as well as with tamoxifen, fulvestrant, exemestane, and exemestane plus everolimus in a letrozole-resistant MCF7 model (MCF7LR). Methods MCF7AC1 tumor-bearing mice were randomized to control (no drug), letrozole (10 μg/day), tamoxifen (500 μg/day), or Z-endoxifen (25 and 75 mg/kg). Treatment in the letrozole arm was continued until resistance developed. MCF7LR tumor-bearing mice were then randomized to Z-endoxifen (50 mg/kg) or tamoxifen for 4 weeks and tumors harvested for microarray and immunohistochemistry analysis. The antitumor activity of Z-endoxifen in the MCF7LR tumors was further compared in a second in vivo study with exemestane, exemestane plus everolimus, and fulvestrant. Results In the MCF7AC1 tumors, both Z-endoxifen doses were significantly superior to control and tamoxifen in reducing tumor volumes at 4 weeks. Additionally, the 75 mg/kg Z-endoxifen dose was additionally superior to letrozole. Prolonged letrozole exposure resulted in resistance at 25 weeks. In MCF7LR tumor-bearing mice, Z-endoxifen significantly reduced tumor volumes compared to tamoxifen, letrozole, and exemestane, with no significant differences compared to exemestane plus everolimus and fulvestrant. Additionally, compared to tamoxifen, Z-endoxifen markedly inhibited ERα target genes, Ki67 and Akt expression in vivo. Conclusion In endocrine-sensitive and letrozole-resistant breast tumors, Z-endoxifen results in robust antitumor and antiestrogenic activity compared to tamoxifen and aromatase inhibitor monotherapy. These data support the ongoing development of Z-endoxifen.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1465-542X
العلاقة: http://link.springer.com/article/10.1186/s13058-020-01286-7Test; https://doaj.org/toc/1465-542XTest
DOI: 10.1186/s13058-020-01286-7
الوصول الحر: https://doaj.org/article/1f0ba8cf46c9435685e14beccf269d8fTest
رقم الانضمام: edsdoj.1f0ba8cf46c9435685e14beccf269d8f
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1465542X
DOI:10.1186/s13058-020-01286-7