Vascular Endothelial Growth Factor (VEGF) Inhibition - A Critical Review

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Vascular Endothelial Growth Factor (VEGF) Inhibition - A Critical Review



Anti-Cancer Agents in Medicinal Chemistry, 7(2): 223-245.

Author(s): Irina Sousa Moreira, Pedro Alexandrino Fernandes and Maria Joao Ramos.

Affiliation: REQUIMTE/Departamento de Quimica, Faculdade de Ciencias da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto - Portugal.

Abstract

Angiogenesis, or formation of new blood capillaries from preexisting vessels, plays both beneficial and damaging roles in the organism. It is a result of a complex balance of positive and negative regulators, and vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic factors involved in tumor angiogenesis. VEGF increases vascular permeability, which might facilitate tumor dissemination via the circulation causing a greater delivery of oxygen and nutrients; it recruits circulating endothelial precursor cells, and acts as a survival factor for immature tumor blood vessels. The endotheliotropic activities of VEGF are mediated through the VEGF-specific tyrosine-kinase receptors: VEGFR-1, VEGFR-2 and VEGFR-3. VEGF and its receptors play a central role in tumor angiogenesis, and therefore the blockade of this pathway is a promising therapeutic strategy for inhibiting angiogenesis and tumor growth. A number of different strategies to inhibit VEGF signal transduction are in development and they include the development of humanized neutralizing anti-VEGF monoclonal antibodies, receptor antagonists, soluble receptors, antagonistic VEGF mutants, and inhibitors of VEGF receptor function. These agents can be divided in two broad classes, namely agents designed to target the VEGF activity and agents designed to target the surface receptor function. The main purpose of this review is to summarize all the available information regarding the importance of the proangiogenic factor VEGF in cancer therapy. After an overview of the VEGF family and their respective receptors, we shall focus our attention on the different VEGF-inhibitors existent nowadays. Agents based upon anti-VEGF therapy have provided solid proofs about their success, and therefore we believe that a critical review is of the utmost importance to help researchers in their future work.

Keywords:

Angiogenesis, VEGF RECEPTORS, Kinase Domain Region, Flt-1D2 domain molecules, Neuropilin-1, Bevacizumab.



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Article Details

Volume: 7
Issue Number: 2
First Page: 223
Last Page: 245
Page Count: 23
DOI: 10.2174/187152007780058687
Price: $58
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