Efficacy and tolerability of AFPep, a cyclic peptide with anti-breast cancer properties
| Autor: | Douglas L. Cohn, Qishan Lin, James A. Bennett, David M. Jones, Tanuj Sharma, Wasila Mansouri, Thomas T. Andersen, Samuel B. Fordyce, Matthew Wu, Paul J. Feustel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Breast Neoplasms Mice SCID Toxicology Peptides Cyclic Rats Sprague-Dawley Mice 03 medical and health sciences Dogs 0302 clinical medicine Therapeutic index Breast cancer In vivo Cell Line Tumor Animals Humans Medicine Pharmacology business.industry Estrogen Antagonists Hep G2 Cells medicine.disease Macaca mulatta Xenograft Model Antitumor Assays Peptide Fragments Rats Tumor Burden AFPep Clinical trial Treatment Outcome 030104 developmental biology Tolerability 030220 oncology & carcinogenesis Hepatocellular carcinoma Toxicity MCF-7 Cells Cancer research Female alpha-Fetoproteins business |
| Zdroj: | Toxicology and Applied Pharmacology. 345:10-18 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2018.03.004 |
| Popis: | Purpose The purpose of this study is to assess the efficacy and safety profile of AFPep, a 9-amino acid cyclic peptide prior to its entry into pre-clinical toxicology analyses en route to clinical trials. Methods AFPep was assessed for anti-estrogenic activity in a mouse uterine growth assay and for breast cancer therapeutic efficacy in a human tumor xenograft model in mice. AFPep was assessed for tolerability in a variety of in vivo models, notably including assessment for effects on rat liver and human hepatocellular carcinoma cell lines and xenografts. Results AFPep arrests the growth of human MCF-7 breast cancer xenografts, inhibits the estrogen-induced growth of mouse uteri, and does not affect liver growth nor stimulate growth of human hepatocellular carcinoma cell lines when growing in vitro or as xenografts in vivo. AFPep is well tolerated in mice, rats, dogs, and primates. Conclusions AFPep is effective for the treatment of ER-positive breast cancer and exhibits a therapeutic index that is substantially wider than that for drugs currently in clinical use. The data emphasize the importance of pursuing pre-clinical toxicology studies with the intent to enter clinical trials. |
| Databáze: | OpenAIRE |
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