ArticleOncotarget2015
Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Clinicopathological and prognostic significance of cyclooxygenase-2 expression in head and neck cancer: A meta-analysis.Oncotarget · 2016Pooled it
- Plasma PlGF as a Potential Biomarker in Ramucirumab-Based Second-Line Therapy for Advanced Gastroesophageal Adenocarcinoma: Exploratory Biomarker Analysis from the Phase II Part of the RAMIRIS Trial.International journal of cancer · 2026Trial
- Cyclooxygenases in pancreatic ductal adenocarcinoma: are they inflammatory catalysts for tumor growth.Frontiers in oncology · 2026Review
- HIF-1α-Mediated Disruption of Cellular Junctions: The Impact of Hypoxia on the Tumor Microenvironment and Invasion.International journal of molecular sciences · 2025Review
- The application and research progress of anti-angiogenesis therapy in tumor immunotherapy.Frontiers in immunology · 2023Review
- Identification of MFGE8 and KLK5/7 as mediators of breast tumorigenesis and resistance to COX-2 inhibition.Breast cancer research : BCR · 2021Article
- Aspirin for the prevention and treatment of pre-eclampsia: A matter of COX-1 and/or COX-2 inhibition?Basic & clinical pharmacology & toxicology · 2020Review
- IRE1α Disruption in Triple-Negative Breast Cancer Cooperates with Antiangiogenic Therapy by Reversing ER Stress Adaptation and Remodeling the Tumor Microenvironment.Cancer research · 2020Article
- Study on the targeted therapy of oral squamous cell carcinoma with a plasmid expressing PE38KDEL toxin under control of the SERPINB3 promoter.Cancer medicine · 2020Article
- Cyclooxygenase-2 Inhibition Potentiates the Efficacy of Vascular Endothelial Growth Factor Blockade and Promotes an Immune Stimulatory Microenvironment in Preclinical Models of Pancreatic Cancer.Molecular cancer research : MCR · 2019Article
- Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis.Oncotarget · 2018Article
- Classical VEGF, Notch and Ang signalling in cancer angiogenesis, alternative approaches and future directions (Review).Molecular medicine reports · 2017Review
- Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B.Nature communications · 2017Article
- Nanoparticles for Targeting Intratumoral Hypoxia: Exploiting a Potential Weakness of Glioblastoma.Pharmaceutical research · 2016Review
- Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis?Oncotarget · 2016Review
- Frizzled-7 promoter is highly active in tumors and promoter-driven Shiga-like toxin I inhibits hepatocellular carcinoma growth.Oncotarget · 2015Article
- Anti-angiogenic efficacy of 5'-triphosphate siRNA combining VEGF silencing and RIG-I activation in NSCLCs.Oncotarget · 2015Article
- Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-angiogenic therapies were approved for different cancers. However, significant primary and secondary resistance hampers efficacy in several tumor types including breast cancer. Thus, we need to develop clinically applicable strategies to enhance efficacy of anti-angiogenic drugs.We report that anti-angiogenic therapies can induce upregulation of cyclooxygenase-2 (Cox-2) and of its product prostaglandin E2 (PGE2) in breast cancer models. Upon Cox-2 inhibition PGE2 levels were normalized and efficacy of anti-vascular endothelial growth factor receptor 2 (anti-VEGFR-2) antibodies and sunitinib was enhanced. Interestingly, both treatments exerted additive anti-angiogenic effects. Following Cox-2 inhibition, we observed reduced infiltration of tumors with cancer-associated fibroblasts (CAFs) and lower levels of pro-angiogenic factors active besides the VEGF axis including hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2). Mechanistic studies indicated that Cox-2 inhibition reduced PGE2-induced migration and proliferation of CAFs via inhibiting phosphorylation of Akt.Hence, Cox-2 inhibition can increase efficacy of anti-angiogenic treatments and our findings might pave the road for clinical investigations of concomitant blockade of Cox-2 and VEGF-signaling.
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Registered trials
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.