ArticleCancer science2017
Targeting of tumor growth and angiogenesis underlies the enhanced antitumor activity of lenvatinib in combination with everolimus.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- A Single-arm, Multicenter, Phase 2 Study of Lenvatinib Plus Everolimus in Patients with Advanced Non-Clear Cell Renal Cell Carcinoma.European urology · 2021Trial
- Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma.British journal of cancer · 2021Trial
- Farnesyl Transferase Inhibitor KO-2806 (Darlifarnib) Enhances the Antitumor Activity of Tyrosine Kinase Inhibitors in RCC.Molecular cancer therapeutics · 2026Article
- A conceptual blueprint for "turning cold to hot" in Osteosarcoma: from TME stratification hypotheses to adaptive therapeutic prospects.Cell communication and signaling : CCS · 2026Review
- PathSynergy: a deep learning model for predicting drug synergy in liver cancer.Briefings in bioinformatics · 2025Article
- PRELP inhibits colorectal cancer progression by suppressing epithelial-mesenchymal transition and angiogenesis via the inactivation of the FGF1/PI3K/AKT pathway.Apoptosis : an international journal on programmed cell death · 2025Article
- Lenvatinib inhibits cholangiocarcinoma progression by targeting the FGF19/PI3K/AKT signaling pathway.Apoptosis : an international journal on programmed cell death · 2025Article
- Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2024Article
- Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.bioRxiv : the preprint server for biology · 2024Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Discovery and Validation of a 15-Gene Prognostic Signature for Clear Cell Renal Cell Carcinoma.JCO precision oncology · 2024Article
- Everolimus in pituitary tumor: a review of preclinical and clinical evidence.Frontiers in endocrinology · 2024Review
- Changes in peripheral blood immune cell population in thyroid cancer patients treated with lenvatinib.Scientific reports · 2023Article
- Angiogenic signaling pathways and anti-angiogenic therapy for cancer.Signal transduction and targeted therapy · 2023Review
- Review
- Immune-awakeninActa pharmaceutica Sinica. B · 2022Article
- Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC.Cellular & molecular biology letters · 2022Article
- Tumor-feeding artery diameter reduction is associated with improved short-term effect of hepatic arterial infusion chemotherapy plus lenvatinib treatment.World journal of gastroenterology · 2022Article
- Efficacy of Nanofiber Sheets Incorporating Lenvatinib in a Hepatocellular Carcinoma Xenograft Model.Nanomaterials (Basel, Switzerland) · 2022Article
- Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies.Expert review of anticancer therapy · 2022Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The combination of lenvatinib, a multiple receptor tyrosine kinase inhibitor, plus everolimus, a mammalian target of rapamycin (mTOR) inhibitor, significantly improved clinical outcomes versus everolimus monotherapy in a phase II clinical study of metastatic renal cell carcinoma (RCC). We investigated potential mechanisms underlying the antitumor activity of the combination treatment in preclinical RCC models. Lenvatinib plus everolimus showed greater antitumor activity than either monotherapy in three human RCC xenograft mouse models (A-498, Caki-1, and Caki-2). In particular, the combination led to tumor regression in the A-498 and Caki-1 models. In the A-498 model, everolimus showed antiproliferative activity, whereas lenvatinib showed anti-angiogenic effects. The anti-angiogenic activity was potentiated by the lenvatinib plus everolimus combination in Caki-1 xenografts, in which fibroblast growth factor (FGF)-driven angiogenesis may contribute to tumor growth. The combination showed mostly additive activity in vascular endothelial growth factor (VEGF)-activated, and synergistic activity against FGF-activated endothelial cells, in cell proliferation and tube formation assays, as well as strongly suppressed mTOR-S6K-S6 signaling. Enhanced antitumor activities of the combination versus each monotherapy were also observed in mice bearing human pancreatic KP-1 xenografts overexpressing VEGF or FGF. Our results indicated that simultaneous targeting of tumor cell growth and angiogenesis by lenvatinib plus everolimus resulted in enhanced antitumor activity. The enhanced inhibition of both VEGF and FGF signaling pathways by the combination underlies its superior anti-angiogenic activity in human RCC xenograft models.
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