ArticleNPJ precision oncology2019
Synchronous inhibition of mTOR and VEGF/NRP1 axis impedes tumor growth and metastasis in renal cancer.
Article in NPJ precision oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- Crosstalk between NRP1 and autophagy in the tumor microenvironment: from molecular mechanisms to therapeutic targeting.Frontiers in immunology · 2026Review
- Upregulated NNMT sustains angiogenesis in clear cell renal cell carcinoma through activation of the SDF-1/CXCR4-ERK-CCL20 axis.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Temporal trends and demographic-geographic disparities in kidney Cancer mortality in the United States, 1999-2023.Preventive medicine reports · 2025Article
- Fibrogenesis-driven tumor progression in clear cell renal cell carcinoma: prognostic, therapeutic implications and the dual role of neuropilin-1.Cancer cell international · 2025Article
- Exploring molecular and cellular mechanisms of Pre-Metastatic niche in renal cell carcinoma.Molecular cancer · 2025Review
- Neuropilin-1: A Multifaceted Target for Cancer Therapy.Current oncology (Toronto, Ont.) · 2025Review
- Advances in immunotherapy and targeted therapy for advanced clear-cell renal cell carcinoma: current strategies and future directions.Frontiers in immunology · 2025Review
- Review
- Targeting mTOR and survivin concurrently potentiates radiation therapy in renal cell carcinoma by suppressing DNA damage repair and amplifying mitotic catastrophe.Journal of experimental & clinical cancer research : CR · 2024Article
- Phase I study of sapanisertib (CB-228/TAK-228/MLN0128) in combination with ziv-aflibercept in patients with advanced solid tumors.Cancer medicine · 2024Article
- Targeting mTOR and Survivin Concurrently Potentiates Radiation Therapy in Renal Cell Carcinoma by Suppressing DNA Damage Repair and Amplifying Mitotic Catastrophe.Research square · 2023Article
- The Nervous System Development Regulator Neuropilin-1 as a Potential Prognostic Marker and Therapeutic Target in Brain Cancer.Cancers · 2023Review
- Exosomes in the Diagnosis and Treatment of Renal Cell Cancer.International journal of molecular sciences · 2023Review
- Article
- NRP1 regulates autophagy and proliferation of gastric cancer through Wnt/β-catenin signaling pathway.Aging · 2023Article
- Everolimus and temsirolimus are not the same second-line in metastatic renal cell carcinoma: a systematic review and meta-analysis.Cost effectiveness and resource allocation : C/E · 2023Review
- Treatment strategies for clear cell renal cell carcinoma: Past, present and future.Frontiers in oncology · 2023Review
- Endothelial VEGFR Coreceptors Neuropilin-1 and Neuropilin-2 Are Essential for Tumor Angiogenesis.Cancer research communications · 2022Article
- TOLLIP Protein Expression Predicts Unfavorable Outcome in Renal Cell Carcinoma.International journal of molecular sciences · 2022Article
- Metastasis prevention: targeting causes and roots.Clinical & experimental metastasis · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Clear cell renal cell carcinoma (ccRCC) is known for its highly vascular phenotype which is associated with elevated expression of vascular endothelial growth factor A (VEGF), also known as vascular permeability factor (VPF). Accordingly, VEGF has been an attractive target for antiangiogenic therapies in ccRCC. Two major strategies have hitherto been utilized for VEGF-targeted antiangiogenic therapies: targeting VEGF by antibodies, ligand traps or aptamers, and targeting the VEGF receptor signaling via antibodies or small-molecule tyrosine-kinase inhibitors (TKIs). In the present article we utilized two entirely different approaches: targeting mammalian target of rapamycin (mTOR) pathway that is known to be involved in VEGF synthesis, and disruption of VEGF/Neuroplin-1 (NRP1) axis that is known to activate proangiogenic and pro-tumorigenic signaling in endothelial and tumor cells, respectively. Everolimus (E) and a small-molecule inhibitor EG00229 (G) were used for the inhibition of mTOR and the disruption of VEGF/NRP1 axis, respectively. We also exploited a liposomal formulation decorated with a proprietary tumor-targeting-peptide (TTP) to simultaneously deliver these two agents in a tumor-targeted manner. The TTP-liposomes encapsulating both Everolimus and EG00229 (EG-L) demonstrated higher in vitro and in vivo growth retardation than the single drug-loaded liposomes (E-L and G-L) in two different ccRCC models and led to a noticeable reduction in lung metastasis in vivo. In addition, EG-L displayed remarkable inhibition of tumor growth in a highly aggressive syngeneic immune-competent mouse model of ccRCC developed in Balb/c mice. Taken together, this study demonstrates an effective approach to achieve improved therapeutic outcome in ccRCC.
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