Abstract
Abstract Despite the continuous research in novel therapeutics, globally each year more people succumb to cancer than HIV, TB and malaria combined. Angiogenesis, the development of neovasculature, has been a major focus of cancer research, and it resulted in the development, approval and clinical use of bevacizumab, an anti-VEGF monoclonal antibody. However, in the case of breast cancer, the results show gains in progression-free survival but not in overall survival. Other agents targeting VEGF receptors are under investigation with the premise that a cocktail of agents could be more effective. Recently, there has been great interest in the development of peptides as therapeutic agents due to their high specificity and low toxicity, which are conducive for the development of new therapeutic cocktails. Identification of pharmacophores (minimal information content) allows for the introduction of non-natural amino acids in the peptide sequence to increase its stability while maintaining or improving its activity, thus creating optimized peptides for clinical applications. We present the application of a 20-mer biomimetic peptide derived from the α5 fibril of collagen IV in which a cysteine is replaced by a non-natural amino acid, i.e., amino-butyric acid, and investigate its mechanism of action as an anti-angiogenic agent in treatment of breast cancer. We demonstrated its activity in suppressing tumor growth in an orthotopic triple negative breast tumor model. In vivo magnetic resonance imaging (MRI) demonstrated reduction in vascular permeability and vascular volume. In vitro studies of receptor pulldown and cellular surface proximity staining demonstrate that this peptide interacts specifically with the αVβ1 integrin. This biomimetic stable peptide is a novel non-VEGF targeting agent active as a single agent, or that could be used in combination with chemotherapy or other therapeutic peptide-based cocktails. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4267. doi:10.1158/1538-7445.AM2011-4267
Published Version
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