VEGF as an inhibitor of tumor vessel maturation: implications for cancer therapy

Area of Science:

• Oncology
• Cancer Biology
• Vascular Biology

Background:

• Tumor angiogenesis, crucial for cancer growth, has been targeted by inhibiting vascular endothelial growth factor (VEGF).
• Anti-VEGF therapies like bevacizumab (Avastin) have shown limited success as monotherapy in human cancers, despite animal model efficacy.
• Combination therapy with chemotherapy yields modest survival benefits, prompting re-evaluation of anti-VEGF mechanisms.

Purpose of the Study:

• To explore the impact of VEGF blockade on tumor vascular maturation.
• To investigate the role of VEGF inhibition in pericyte activation and vascular normalization.
• To consider the implications of these findings for developing novel cancer therapies.

Main Methods:

• Review of recent scientific literature on VEGF blockade and tumor microenvironment.
• Analysis of studies investigating the effects of anti-VEGF agents on mural cells and pericytes.
• Synthesis of data on VEGF signaling, platelet-derived growth factor (PDGF) responsiveness, and vascular maturation.

Main Results:

• VEGF blockade can unexpectedly activate mural cells/pericytes, leading to vascular normalization and maturation.
• High VEGF levels in tumors may decrease mural cell responsiveness to PDGF.
• Anti-VEGF agents may promote vascular maturation, a critical effect beyond simple anti-angiogenesis.

Conclusions:

• VEGF blockade's impact extends beyond inhibiting vessel growth to include vascular maturation via pericyte activation.
• Understanding these complex effects is crucial for optimizing anti-VEGF strategies in cancer treatment.
• Targeting VEGF may offer a dual approach: inhibiting angiogenesis and promoting vascular normalization for improved therapeutic outcomes.