Human epidermal growth factor receptor 2 (HER2) extracellular domain III and Vascular endothelial growth factor (VEGF) (HER2-VEGF)

The target "HER2 extracellular domain III and VEGF" refers to a dual-therapeutic strategy designed to simultaneously inhibit the Human Epidermal Growth Factor Receptor 2 (HER2) and the Vascular Endothelial Growth Factor (VEGF). HER2 is a receptor tyrosine kinase that, when overexpressed or amplified, drives aggressive tumor growth and survival through the PI3K/Akt and MAPK pathways [1, 7]. VEGF is a potent pro-angiogenic growth factor that stimulates the formation of new blood vessels, which are essential for tumor nutrient supply and metastasis [3, 16]. Research indicates a strong correlation between HER2 signaling and the upregulation of VEGF, suggesting that dual inhibition can provide synergistic anti-tumor effects and overcome resistance to single-agent therapies [2, 16]. Bispecific antibodies, such as YY0411 and the VHS platform, have been engineered to bind specifically to the extracellular domain III of HER2 while sequestering soluble VEGF [4, 6]. This approach not only blocks oncogenic signaling and angiogenesis but can also enhance immune-mediated mechanisms like antibody-dependent cellular phagocytosis (ADCP) [6]. Clinically, the combination of separate HER2 and VEGF inhibitors (e.g., trastuzumab and bevacizumab) has been explored to improve outcomes in HER2-positive metastatic breast cancer [1, 5].

Other names

HER2/VEGFErbB2/VEGFAHER2-VEGF bispecific targetHER2 domain III and VEGF-A

Simultaneous inhibition of HER2-mediated signaling and VEGF-induced angiogenesis.