ArticleMedical oncology (Northwood, London, England)2021
The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors.
Article in Medical oncology (Northwood, London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 66 citations in OpenAlex.
- Efficacy of lenvatinib combined with sintilimab and transcatheter arterial chemoembolization in conversion therapy for unresectable hepatocellular carcinoma.Pakistan journal of medical sciences · 2026Article
- Rechallenge with Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma: A Narrative Review.Liver cancer · 2026Review
- Ultrasound-targeted cavitation induced tumor vascular normalization and radiotherapy sensitization in breast cancer.Science China. Life sciences · 2026Article
- Review
- Anlotinib plus whole-brain radiotherapy for NSCLC brain metastases: a prospective, non-randomized, single-center cohort study.Scientific reports · 2026Article
- TACE and tyrosine kinase inhibitors with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC: a multicenter real-world cohort study.Hepatology international · 2026Article
- Transarterial infusion chemotherapy combined with lenvatinib and tislelizumab versus intravenous chemotherapy for unresectable pancreatic ductal adenocarcinoma: a retrospective propensity score matching analysis.Frontiers in oncology · 2026Article
- Local Tumor Response to Conventional Transarterial Chemoembolization following Seven-day Lenvatinib Administration.Interventional radiology (Higashimatsuyama-shi (Japan) · 2026Article
- A Retrospective Study of Hepatic Arterial Infusion Chemotherapy Combined with Tyrosine Kinase Inhibitors and PD-1 Inhibitors in Hepatocellular Carcinoma Patients with Main Portal Vein Tumor Thrombus (VP4).Journal of hepatocellular carcinoma · 2026Article
- Article
- Mechanical properties of the tumor microenvironment: drivers of immunotherapy resistance in solid tumors.Frontiers in immunology · 2026Review
- SIRT or TACE in combination with Lenvatinib and PD-(L)1 inhibitor in high tumor burden hepatocellular carcinoma: a multicenter, retrospective, propensity score-matched study.International journal of surgery (London, England) · 2025Article
- Efficacy and safety analysis of D-TACE combined with lenvatinib in the treatment of hepatocellular carcinoma refractory to C-TACE.BMC gastroenterology · 2025Article
- Anlotinib promotes CD4 + T cell infiltration and enhances the anti-tumor effect of PD-1 blockade in lung cancer.Immunologic research · 2025Article
- Sonographic evaluation of vascular normalization induced by lenvatinib in a patient with hepatocellular carcinoma.Journal of medical ultrasonics (2001) · 2025Article
- Lenvatinib in combination with radiotherapy versus lenvatinib with transarterial chemoembolization for advanced hepatocellular carcinoma.BMC cancer · 2025Article
- Advances in Systemic Therapy for Hepatocellular Carcinoma and Future Prospects.Current oncology (Toronto, Ont.) · 2025Review
- Transarterial Chemoembolization for Hepatocellular Carcinoma: Current Role and Techniques.Interventional radiology (Higashimatsuyama-shi (Japan) · 2025Review
- Systemic Therapy Combined with Locoregional Therapy in Intermediate-stage Hepatocellular Carcinoma.Interventional radiology (Higashimatsuyama-shi (Japan) · 2025Review
- Vascular Endothelial Growth Factor Receptors in the Vascularization of Pancreatic Tumors: Implications for Prognosis and Therapy.Current issues in molecular biology · 2025Review
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The evaluation of angiogenesis inhibitors requires the analysis of the precise structure and function of tumor vessels. The anti-angiogenic agents lenvatinib and sorafenib are multi-target tyrosine kinase inhibitors that have been approved for the treatment of hepatocellular carcinoma (HCC). However, the different effects on tumor vasculature between lenvatinib and sorafenib are not well understood. In this study, we analyzed the effects of both drugs on vascular structure and function, including vascular normalization, and investigated whether the normalization had a positive effect on a combination therapy with the drugs and radiation using micro X-ray computed tomography with gold nanoparticles as a contrast agent, as well as immunohistochemical analysis and interstitial fluid pressure (IFP) measurement. In mice subcutaneously transplanted with mouse HCC cells, treatment with lenvatinib or sorafenib for 14 days inhibited tumor growth and reduced the tumor vessel volume density. However, analysis of integrated data on vessel density, rates of pericyte-covering and perfused vessels, tumor hypoxia, and IFP measured 4 days after drug treatment showed that treatment with 3 mg/kg of lenvatinib significantly reduced the microvessel density and normalized tumor vessels compared to treatment with 50 mg/kg of sorafenib. These results showed that lenvatinib induced vascular normalization and improved the intratumoral microenvironment in HCC tumors earlier and more effectively than sorafenib. Moreover, such changes increased the radiosensitivity of tumors and enhanced the effect of lenvatinib and radiation combination therapy, suggesting that this combination therapy is a powerful potential application against HCC.
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