Abstract
Tumor angiogenesis is a key event that governs tumor progression and metastasis. It is controlled by the complicated and coordinated actions of pro-angiogenic factors and their receptors that become upregulated during tumorigenesis. Over the past several decades, vascular endothelial growth factor (VEGF) signaling has been identified as a central axis in tumor angiogenesis. The remarkable advent of recombinant antibody technology has led to the development of bevacizumab, a humanized antibody that targets VEGF and is a leading clinical therapy to suppress tumor angiogenesis. However, despite the clinical efficacy of bevacizumab, its significant side effects and drug resistance have raised concerns necessitating the identification of novel drug targets and development of novel therapeutics to combat tumor angiogenesis. This review will highlight the role and relevance of VEGF and other potential therapeutic targets and their receptors in angiogenesis. Simultaneously, we will also cover the current status of monoclonal antibodies being developed to target these candidates for cancer therapy.
Highlights
Angiogenesis is a physiological process in which new blood vessels are formed from pre-existing vessels
vascular endothelial growth factor (VEGF)-C or VEGF-D activation of VEGF receptors (VEGFRs)-3 plays a critical role in lymphangiogenesis; in lymphatic endothelial cells, SHC and growth factor receptor bound protein 2 (GRB2) adaptor proteins are recruited to activated VEGFR-3 and promote ERK1/2 and PI3K/Akt murine thymoma viral (Akt) pathway, which is critical for lymphatic endothelial cell migration [41,42]
Anti-angiogenesis strategies using monoclonal antibodies have been effective in suppressing tumor progression and metastasis in combination with chemotherapy
Summary
Angiogenesis is a physiological process in which new blood vessels are formed from pre-existing vessels. Bevacizumab, an anti-VEGF antibody, was recently developed as a cancer therapy to suppress tumor angiogenesis [16,17]. Action of therapeutic antibodies being developed for anti-angiogenic therapy (Figures 1 and 2) When these molecules bindthese theirmolecules cognate receptors, receptor dimerization and autophosphorylation autophosphorylation stimulate downstream signaling molecules stimulate downstream signaling molecules including phosphatidylinositol-4,5-bisphosphateincluding.
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