Current Protein-based Anti-angiogenic Therapeutics
Colin J. Barrow,
Rupinder K. Kanwar,
Jagat R. Kanwar.
Angiogenesis is a multistep process for the formation of new blood vessels. Interactions between several
cellular factors including growth factors, cytokines and hematopoietic factors lead to activation of various cellular
pathways finally resulting in the extracellular matrix (ECM) degradation, endothelial cell proliferation, survival and
migration. Normally, angiogenesis is an essential requirement for vascular development in growing embryos as well as in
adult tissues where this process depends on the intricate balance between the activities of the pro- and anti-angiogenic
factors. Abnormal angiogenesis results in aberrant vasculature leading to various pathological conditions. The most
important factor implicated in angiogenic processes is vascular endothelial growth factor (VEGF) and its family of ligands
and receptors. Several anti-angiogenic drugs have been developed and many more are currently in different phases of
clinical trials, which target various angiogenesis-inducing agents including VEGF, VEGF receptors, angiopoietins and
ECM components such as integrins. Anti-angiogenic therapy can be divided into gene-based therapy and protein-based
therapy. Gene-based therapies include the use of antisense oligonucleotides, siRNA, aptamers, catalytic oligonucleotides
including ribozymes and DNAzymes and transcription decoys. Protein-based therapeutics includes monoclonal
antibodies, peptidomimetics, fusion proteins and decoy receptors. The later class of therapeutics has several advantages
over gene-based and small molecule drugs, including specificity and complexity in functions, better tolerability, less
interference with normal biological processes and lesser adverse effects due to decreased immune response by virtue of
being mostly body’s natural proteins. This review provides a comprehensive overview of angiogenesis and on the current
protein-based anti-angiogenic therapeutics under research and in the clinic.
Keywords: Angiogenesis, anti-angiogenic drugs, clinical trials, Fc-fusion proteins, VEGF, VEGF receptors.
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