Dual blockade of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) exhibits potent...

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) are key drivers of angiogenesis and cancer progression.
• Resistance to anti-VEGF therapies can arise from compensatory upregulation of other pro-angiogenic factors like FGF-2.

Purpose of the Study:

• To develop and evaluate a novel chimeric decoy receptor, VF-Trap, for simultaneous blockade of VEGF and FGF-2 signaling pathways.
• To assess the additive or synergistic anti-tumor and anti-angiogenic effects of VF-Trap in vitro and in vivo.

Main Methods:

• In vitro studies using endothelial cells to assess the impact of VF-Trap on proliferation and migration induced by VEGF and FGF-2.
• In vivo studies using xenograft tumor models and a mouse oxygen-induced retinopathy (OIR) model to evaluate anti-tumor and anti-angiogenic efficacy.

Main Results:

• VF-Trap demonstrated potent inhibition of VEGF- and FGF-2-induced endothelial cell proliferation and migration in vitro.
• VF-Trap significantly inhibited xenograft tumor growth and ocular angiogenesis in mouse models, outperforming single-pathway blockers.
• The fusion protein showed potent anti-angiogenic effects by blocking both VEGF and FGF-2 activity.

Conclusions:

• The novel VF-Trap fusion protein effectively targets both VEGF and FGF-2 pathways, exhibiting significant anti-angiogenic and anti-tumor activity.
• VF-Trap represents a promising therapeutic candidate for angiogenesis-related diseases, including cancer and ocular vascular disorders.