Ang2 regulated VEGF expression at the transcriptional level in relation to a decrease in hypoxia-inducible factor (HIF)-1α expression and HIF-DNA–binding activity. Tie2 silencing by small interfering RNA (siRNA) rescued the Ang2-mediated down-modulation of VEGF, suggesting an essential role for Tie2 in this regulatory loop .

Because Ang2 is expressed in growing blood vessels and promotes angiogenesis driven by vascular endothelial growth factor (VEGF), we asked whether the anti-tumor effect of Ang2 inhibition results from reduced sprouting angiogenesis and whether the effect is augmented by inhibition of VEGF from tumor cells.

Adjuvant Ang2 inhibition was most effective when combined with VEGF-A neutralization (via the bispecific anti-Ang2/VEGF-A agent, CVX-241) in 2 breast cancer models. On the contrary, adjuvant Ang2 inhibition was optimal when combined with VEGFR2 TKI therapy (via CVX-060 + sunitinib) in a renal cancer model.

2023年12月20日 · Two distinct strategies were used to target the ANG2/TIE2 and VEGF/VEGFR2 pathways. The first combination used a modified antibody that was ANG2-specific (CVX-060) and a small-molecule VEGFR2 TKI (such as sunitinib or regorafenib). In the second strategy, CVX-241, a single agent that is bispecific for both ANG2 and VEGF-A, was used [151]. In ...

It is reported that the treatment effect of patients can be improved by adding bevacizumab to the chemotherapy regimen of metastatic colorectal cancer (such as 5-FU and irinotecan) to inhibit vascular endothelial growth factor (VEGF) .

2014年8月7日 · We employed late-stage RIP1-Tag2 pancreatic neuroendocrine tumors (PNETs) and MMTV-PyMT mammary adenocarcinomas, which develop resistance to VEGF receptor 2 (VEGFR2) blockade. We found that VEGFR2 inhibition upregulated ANG2 and vascular TIE2 and enhanced infiltration by TIE2-expressing macrophages in the PNETs.

2011年7月1日 · The inhibition of Ang2 results in the normalization of the aberrant tumor vessel phenotype and reduced blood vessel sprouting, whereas Ang1 inhibition prevents the normalization induced by Ang2 inhibition.

This article discusses recent studies of Ang2 in angiogenesis and the implication of Ang2 as a therapeutic target as well as a potential inhibitor for antiangiogenesis treatment for cancer patients.

2015年1月6日 · Effective vascular normalisation following vascular endothelial growth factor (VEGF) inhibition is associated with endothelial cell regression leaving empty basement membrane...

Here we show that dual inhibition of VEGFRs and Ang-2 inhibits tumor growth and prolongs vessel normalization compared with VEGFR inhibition alone, resulting in improved survival in murine GBM models. Furthermore, by blocking macrophage recruitment, we demonstrate that macrophages contribute to the beneficial effects of dual therapy.