VEGF/VEGFR pathway inhibitors as anti-angiogenic agents: present and future - PubMed (original) (raw)
Review
VEGF/VEGFR pathway inhibitors as anti-angiogenic agents: present and future
P Sapra Sharma et al. Curr Cancer Drug Targets. 2011 Jun.
Abstract
Angiogenesis, the formation of new blood vessels from pre-existing ones, plays a central role in the process of tumor growth and metastasis. The proliferation of endothelium and formation of new blood vessels further the size of solid tumors. It is expected that blocking angiogenesis will be an efficient therapeutic approach against many tumor types. The key signaling system that regulates proliferation and migration of endothelial cells are vascular endothelium growth factor (VEGF) and their receptors (VEGFR-1, -2 and -3). VEGFR-2, a receptor with higher affinity and greater kinase activity, is more important in the direct regulation of angiogenesis, mitogenic signaling, and permeability-enhancing effects. VEGFRs are expressed at high levels in many types of human solid tumors, including glioma, lung, breast, renal, ovarian and gastrointestinal tract carcinomas. Inhibition of VEGFR has emerged as a potential therapy method for cancers and it has been clinically validated with FDA-approvals of bevacizumab, sorafenib, and suntinib. Consequently, a number of small molecules with VEGFR inhibitory properties have been developed. Many of these have been evaluated as potent inhibitors and some are currently in clinical-trials for various angiogenic related disorders including inflammatory diseases, retinopathies and age related macular degeneration. This review reports various VEGF/VEGFR pathway inhibitors such as small molecules and monoclonal antibodies, along with their reported activities.
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