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Trends in Cancer Research   Volumes    Volume 15 
Tolerability and efficacy of AFPep in multiple models of breast cancer including spontaneous canine mammary cancer
Kanthi Bommareddy, Ann Hohenhaus, Roman Ginnan, Priya Shivraj, Thomas T. Andersen, James A. Bennett
Pages: 17 - 25
Number of pages: 9
Trends in Cancer Research
Volume 15 

Copyright © 2020 Research Trends. All rights reserved

AFPep is a 9-amino acid, cyclic peptide derivative of the anti-estrogenic/anti-breast cancer active site of alpha-fetoprotein [AFP]. The purpose of this study was to determine the tolerability of AFPep in normal and tumor-bearing dogs and assess its effect on biomarkers of estrogen-promoted growth in several models of breast cancer. Fourteen normal beagle dogs were treated with various doses of AFPep through i.v., s.c., and p.o. routes. Blood levels of AFPep and clinical signs of tolerability were monitored. Expression of ERα, pERα, TRIM25, and KLF5 were assessed in three estrogen-sensitive tissue models: immature mouse uterus, MCF7 xenografts, and spontaneous canine mammary tumors excised from AFPep-treated animals. In normal and tumor-bearing dogs, AFPep was well tolerated at all doses and through all routes. Uteri and MCF7 xenografts from mice treated with AFPep were growth-inhibited with suppression of the aforementioned biomarkers. In tumor-bearing dogs, one of six dogs had tumors expressing ERα. In that animal, AFPep resulted in a decrease in the expression of KLF5 and TRIM25 as well as a decrease in the ratio of pERα/Total ERα in tumor tissue compared to pre-treatment levels in tumor samples from the same animal. AFPep is well tolerated in multiple animal models, inhibits estrogen-mediated growth, and decreases pERα/ERα, KLF5 and TRIM25 expression.
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