2-(ω-Carboxyethyl)pyrrole Antibody as a New Inhibitor of Tumor Angiogenesis and Growth

Title:2-(ω-Carboxyethyl)pyrrole Antibody as a New Inhibitor of Tumor Angiogenesis and Growth

Volume: 17 Issue: 6

Author(s): Chunying Wu, Xizhen Wang, Nicholas Tomko, Junqing Zhu, William R. Wang, Jinle Zhu, Bin Wangf, Yanming Wang*Robert G. Salomon*

Affiliation:

• Department of Radiology, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106,United States

• Chemistry, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106,United States

Keywords: Angiogenesis inhibitors, vascular endothelial growth factor (VEGF), bevacizumab, 2-(ω-carboxyethyl)pyrrole (CEP), positron emission tomography (PET), and imaging.

Abstract: Background: Angiogenesis is a fundamental process in the progression, invasion, and metastasis of tumors. Therapeutic drugs such as bevacizumab and ranibuzumab have thus been developed to inhibit vascular endothelial growth factor (VEFG)-promoted angiogenesis. While these anti-angiogenic drugs have been commonly used in the treatment of cancer, patients often develop significant resistance that limits the efficacy of anti-VEGF therapies to a short period of time. This is in part due to the fact that an independent pathway of angiogenesis exists, which is mediated by 2-(ω-carboxyethyl)pyrrole (CEP) in a TLR2 receptor-dependent manner that can compensate for inhibition of the VEGF-mediated pathway.

Aims: In this work, we evaluated a CEP antibody as a new tumor growth inhibitor that blocks CEP-induced angiogenesis.

Method: We first evaluated the effectiveness of a CEP antibody as a monotherapy to impede tumor growth in two human tumor xenograft models. We then determined the synergistic effects of bevacizumab and CEP antibody in a combination therapy, which demonstrated that blocking of the CEP-mediated pathway significantly enhanced the anti-angiogenic efficacy of bevacizumab in tumor growth inhibition indicating that CEP antibody is a promising chemotherapeutic drug. To facilitate potential translational studies of CEP-antibody, we also conducted longitudinal imaging studies and identified that FMISO-PET is a non-invasive imaging tool that can be used to quantitatively monitor the anti-angiogenic effects of CEP-antibody in the clinical setting.

Results: That treatment with CEP antibody induces hypoxia in tumor tissue WHICH was indicated by 43% higher uptake of [18F]FMISO in CEP antibody-treated tumor xenografs than in the control PBS-treated littermates.

Cite this article as:

Wu Chunying, Wang Xizhen, Tomko Nicholas, Zhu Junqing, Wang R. William, Zhu Jinle, Wangf Bin, Wang Yanming*, Salomon G. Robert*, 2-(ω-Carboxyethyl)pyrrole Antibody as a New Inhibitor of Tumor Angiogenesis and Growth, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (6) . https://dx.doi.org/10.2174/1871520616666160923093959

DOI https://dx.doi.org/10.2174/1871520616666160923093959	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992