ArticleCancer biology & therapy2014
The vascular disrupting agent BNC105 potentiates the efficacy of VEGF and mTOR inhibitors in renal and breast cancer.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Bevacizumab plus fosbretabulin in recurrent ovarian cancer: Overall survival and exploratory analyses of a randomized phase II NRG oncology/gynecologic oncology group study.Gynecologic oncology · 2020Trial
- A Phase I/II Trial of BNC105P with Everolimus in Metastatic Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
- Evaluating Therapeutic Efficacy of the Vascular Disrupting Agent OXi8007 Against Kidney Cancer in Mice.Cancers · 2025Article
- Article
- Nanoparticle-Based Therapeutics to Overcome Obstacles in the Tumor Microenvironment of Hepatocellular Carcinoma.Nanomaterials (Basel, Switzerland) · 2022Review
- The molecular underpinning of geminin-overexpressing triple-negative breast cancer cells homing specifically to lungs.Cancer gene therapy · 2022Article
- Non-Invasive Evaluation of Acute Effects of Tubulin Binding Agents: A Review of Imaging Vascular Disruption in Tumors.Molecules (Basel, Switzerland) · 2021Review
- A Glimpse in the Future of Malignant Mesothelioma Treatment.Frontiers in pharmacology · 2021Review
- Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds.International journal of molecular sciences · 2020Review
- Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma.BMC cancer · 2020Article
- mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia.Molecular medicine reports · 2018Article
- Targeting VEGF pathway to normalize the vasculature: an emerging insight in cancer therapy.OncoTargets and therapy · 2018Review
- Angiogenic factors are increased in circulating granulocytes and CD34Molecular carcinogenesis · 2017Article
- Correlation of genetic polymorphism of vascular endothelial growth factor gene with susceptibility to lung cancer.Cancer gene therapy · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BNC105 is a tubulin targeting compound that selectively disrupts vasculature within solid tumors. The severe tumor hypoxia and necrosis that ensues translates to short term tumor growth inhibition. We sought to identify the molecular and cellular events activated following BNC105 treatment that drives tumor recovery. We investigated tumor adaptation to BNC105-induced hypoxia in animal models of breast and renal cancer. HIF-1α and GLUT-1 were found to be strongly upregulated by BNC105 as was the VEGF signaling axis. Phosphorylation of mTOR, 4E-BP-1 and elF2α were upregulated, consistent with increased protein synthesis and increased expression of VEGF-A. We sought to investigate the potential therapeutic utility of combining BNC105 with agents targeting VEGF and mTOR signaling. Bevacizumab and pazopanib target the VEGF axis and have been approved for first line use in renal cancer. Everolimus targets mTOR and is currently approved in second line therapy of renal and particular breast cancers. We combined these agents with BNC105 to explore the effects on tumor vasculature, tumor growth inhibition and animal survival. Bevacizumab hindered tumor vascular recovery following BNC105 treatment leading to greater tumor growth inhibition in a breast cancer model. Consistent with this, addition of BNC105 to pazopanib treatment resulted in a significant increase in survival in an orthotopic renal cancer model. Combination treatment of BNC105 with everolimus also increased tumor growth inhibition. BNC105 is currently being evaluated in a randomized phase II clinical trial in combination with everolimus in renal cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.