ArticleCancer science2014
Lenvatinib in combination with golvatinib overcomes hepatocyte growth factor pathway-induced resistance to vascular endothelial growth factor receptor inhibitor.
Article in Cancer science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Hypoxia-induced endoplasmic reticulum stress mediates lenvatinib resistance in hepatocellular carcinoma through the IRE1α-XBP1s-HIF1α pathway.Journal of cancer research and clinical oncology · 2026Article
- Dual-drug loaded chondroitin sulfate embolization beads enhance TACE therapy for HCC by integrating embolization, chemotherapy, and anti-angiogenesis.Materials today. Bio · 2025Article
- Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.Medical oncology (Northwood, London, England) · 2024Review
- Insight in Quinazoline-based HDAC Inhibitors as Anti-cancer Agents.Mini reviews in medicinal chemistry · 2024Review
- Design, Synthesis, and Anti-Cervical Cancer and Reversal of Tumor Multidrug Resistance Activity of Novel Nitrogen-Containing Heterocyclic Chalcone Derivatives.Molecules (Basel, Switzerland) · 2023Article
- Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti-PD-1 Antibody.Molecular cancer therapeutics · 2023Article
- Design, construction and in vivo functional assessment of a hinge truncated sFLT01.Gene therapy · 2023Article
- Synergistic Effect of Lenvatinib and Chemotherapy in Hepatocellular Carcinoma Using Preclinical Models.Journal of hepatocellular carcinoma · 2023Article
- Combination of Vitamin C and Lenvatinib potentiates antitumor effects in hepatocellular carcinoma cellsPeerJ · 2023Article
- The antiviral activity of a small molecule drug targeting the NSP1-ribosome complex against Omicron, especially in elderly patients.Frontiers in cellular and infection microbiology · 2023Article
- Lenvatinib resistance mechanism and potential ways to conquer.Frontiers in pharmacology · 2023Review
- Dexamethasone and lenvatinib inhibit migration and invasion of non-small cell lung cancer by regulating EKR/AKT and VEGF signal pathways.Experimental and therapeutic medicine · 2020Article
- Lenvatinib promotes antitumor immunity by enhancing the tumor infiltration and activation of NK cells.American journal of cancer research · 2019Article
- Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment.Cancer management and research · 2019Review
- MET/HGF pathway activation as a paradigm of resistance to targeted therapies.Annals of translational medicine · 2017Review
- A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma.Genome medicine · 2016Article
- Spotlight on lenvatinib in the treatment of thyroid cancer: patient selection and perspectives.Drug design, development and therapy · 2016Review
- Multitargeting strategy using lenvatinib and golvatinib: maximizing anti-angiogenesis activity in a preclinical cancer model.Cancer science · 2015Article
- Article
- Redundant kinase activation and resistance of EGFR-tyrosine kinase inhibitors.American journal of cancer research · 2014Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor receptor (VEGFR) inhibitors are approved for the treatment of several tumor types; however, some tumors show intrinsic resistance to VEGFR inhibitors, and some patients develop acquired resistance to these inhibitors. Therefore, a strategy to overcome VEGFR inhibitor resistance is urgently required. Recent reports suggest that activation of the hepatocyte growth factor (HGF) pathway through its cognate receptor, Met, contributes to VEGFR inhibitor resistance. Here, we explored the effect of the HGF/Met signaling pathway and its inhibitors on resistance to lenvatinib, a VEGFR inhibitor. In in vitro experiments, addition of VEGF plus HGF enhanced cell growth and tube formation of HUVECs when compared with stimulation by either factor alone. Lenvatinib potently inhibited the growth of HUVECs induced by VEGF alone, but cells induced by VEGF plus HGF showed lenvatinib resistance. This HGF-induced resistance was cancelled when the Met inhibitor, golvatinib, was added with lenvatinib. Conditioned medium from tumor cells producing high amounts of HGF also conferred resistance to inhibition by lenvatinib. In s.c. xenograft models based on various tumor cell lines with high HGF expression, treatment with lenvatinib alone showed weak antitumor effects, but treatment with lenvatinib plus golvatinib showed synergistic antitumor effects, accompanied by decreased tumor vessel density. These results suggest that HGF from tumor cells confers resistance to tumor endothelial cells against VEGFR inhibitors, and that combination therapy using VEGFR inhibitors with Met inhibitors may be effective for overcoming resistance to VEGFR inhibitors. Further evaluation in clinical trials is warranted.
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