Rapid decrease in tumor perfusion following VEGF blockade predicts long-term tumor growth inhibition in preclinical...

Area of Science:

• Oncology
• Vascular Biology
• Medical Imaging

Background:

• Vascular endothelial growth factor (VEGF) drives tumor angiogenesis, but not all tumors respond to VEGF blockade.
• Identifying early biomarkers for anti-VEGF therapy efficacy remains challenging due to unclear functional effects on tumor vasculature.

Purpose of the Study:

• To assess rapid molecular, morphologic, and functional vascular responses to aflibercept in preclinical tumor models.
• To correlate these early vascular changes with long-term tumor growth inhibition.

Main Methods:

• Utilized preclinical tumor models (Colo205, C6, HT1080) with varying sensitivities to anti-VEGF therapy.
• Administered aflibercept and assessed tumor vascular responses using dynamic contrast-enhanced ultrasound (DCE-US) for perfusion, gene expression, and microvessel density.
• Correlated vascular changes with long-term tumor growth inhibition.

Main Results:

• Decreased tumor vessel perfusion (DCE-US) and increased tumor hypoxia correlated strongly with long-term tumor growth inhibition.
• Changes in vascular gene expression and microvessel density did not correlate with long-term efficacy.
• Findings align with clinical studies linking decreased perfusion to anti-VEGF therapy response.

Conclusions:

• Early assessment of tumor perfusion using DCE-US after anti-VEGF therapy can predict treatment efficacy.
• Tumor perfusion changes are a more reliable early biomarker than vascular gene expression or microvessel density.
• This approach may be valuable for predicting response to VEGF inhibitors and other anti-angiogenic therapies.