The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors

The evaluation of angiogenesis inhibitors requires the analysis precise structure and function tumor vessels. anti-angiogenic agents lenvatinib sorafenib are multi-target tyrosine kinase that have been approved for treatment hepatocellular carcinoma (HCC). However, different effects on vasculature between not well understood. In this study, we analyzed both drugs vascular function, including normalization, investigated whether normalization had a positive effect combination therapy with radiation using micro X-ray computed tomography gold nanoparticles as contrast agent, immunohistochemical interstitial fluid pressure (IFP) measurement. mice subcutaneously transplanted mouse HCC cells, or 14 days inhibited growth reduced vessel volume density. integrated data density, rates pericyte-covering perfused vessels, hypoxia, IFP measured 4 after drug showed 3 mg/kg significantly microvessel density normalized vessels compared to 50 sorafenib. These results induced improved intratumoral microenvironment in tumors earlier more effectively than Moreover, such changes increased radiosensitivity enhanced therapy, suggesting is powerful potential application against HCC.