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Anti-angiogenic Targets: Angiopoietin and Angiopoietin Receptors


ABSTRACT: Tumor blood vessel formation (angiogenesis) is essential for tumor growth and metastasis. Two main endothelial ligand–receptor pathways regulating angiogenesis are vascular endothelial growth factor (VEGF) receptor and angiopoietin-TIE receptor pathways. The angiopoietin-TIE pathway is required for the remodeling and maturation of the blood and lymphatic vessels during embryonic development after VEGF and VEGF-C mediated development of the primary vascular plexus. Angiopoietin-1 (ANGPT1) stabilizes the vasculature after angiogenic processes, via tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE2) activation. In contrast, ANGPT2 is upregulated at sites of vascular remodeling. ANGPT2 is secreted by activated endothelial cells in inflammation, promoting vascular destabilization. ANGPT2 has been found to be expressed in many human cancers. Intriguingly, in preclinical models inhibition of ANGPT2 has provided promising results in preventing tumor angiogenesis, tumor growth, and metastasis, making it an attractive candidate to target in tumors. However, until now the first ANGPT2 targeting therapies have been less effective in clinical trials than in experimental models. Additionally, in preclinical models combined therapy against ANGPT2 and VEGF or immune checkpoint inhibitors has been superior to monotherapies, and these pathways are also targeted in early clinical trials. In order to improve current anti-angiogenic therapies and successfully exploit ANGPT2 as a target for cancer treatment, the biology of the angiopoietin-TIE pathway needs to be profoundly clarified.

SUBMITTER: Marme D 

PROVIDER: S-EPMC7124104 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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