ArticleCancer research communications2023
Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Antitumor Activity Against Prostaglandin-Expressing Tumors.
Article in Cancer research communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 35 citations in OpenAlex.
- First-in-human phase I study of DT-9081, a selective EP4 receptor antagonist, in advanced solid tumors.Investigational new drugs · 2026Article
- Platelet-neutrophil cooperation in cancer: mechanisms of metastatic niche formation and implications for prognostic stratification and therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Decoding GPCR signaling reprogramming in cancer: molecular mechanisms and therapeutic implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Ablation of prostaglandin ENature biomedical engineering · 2026Article
- Donor age and sex program MSC secretome signaling: a quadrant framework for precision therapy.Stem cell research & therapy · 2026Article
- Tumor Extracellular Vesicles lncOSLMT Drives Lung Inflammatory Premetastatic Niche Formation in Osteosarcoma via mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting inflammatory microenvironments: overcoming therapy resistance and immunosuppression.Molecular cancer · 2026Review
- Stage-Dependent Role of Eicosanoids in Colorectal Cancer.International journal of molecular sciences · 2026Article
- Mast cell driven immunometabolism as a therapeutic entry point in ESCC.Frontiers in cell and developmental biology · 2026Review
- Metabolic reprogramming networks in the gastric cancer tumor microenvironment: an integrated axis of nutrient competition, metabolic crosstalk, and immunosuppression.Frontiers in immunology · 2026Review
- Engineering with EP2/EP4 knockout and IL-15 transpresentation renders stem cell-derived NK cells self-persistent and resistant to PGE2 inhibition.Frontiers in immunology · 2026Article
- Lipid metabolism and the immune microenvironment in gastric cancer.Frontiers in immunology · 2026Review
- Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026Review
- Conventional and alternative approaches for targeting PIK3CA and PTEN alterations in head and neck, breast, and other cancers.Advances in biological regulation · 2026Review
- Targeting Lipid Metabolic Reprogramming to Overcome Immunotherapy Resistance: Systemic Nutritional Modulation and Precision Nanomedicine.International journal of nanomedicine · 2026Review
- Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer.Journal of ovarian research · 2025Article
- The Phenotypical and Functional Effect of PGE2 on Human Macrophages.European journal of immunology · 2025Article
- Contribution of Prostaglandin E2-Induced Neuronal Excitation to Drug Resistance in Glioblastoma Countered by a Novel Blood-Brain Barrier Crossing Celecoxib Derivative.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A CD4Immunity · 2025Article
- Blockade of the PGE2 Pathway Inhibits the Growth of PTEN-Deficient HNSCC Tumors.Molecular cancer therapeutics · 2025Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While the role of prostaglandin E2 (PGE2) in promoting malignant progression is well established, how to optimally block the activity of PGE2 signaling remains to be demonstrated. Clinical trials with prostaglandin pathway targeted agents have shown activity but without sufficient significance or dose-limiting toxicities that have prevented approval. PGE2 signals through four receptors (EP1-4) to modulate tumor progression. EP2 and EP4 signaling exacerbates tumor pathology and is immunosuppressive through potentiating cAMP production. EP1 and EP3 signaling has the opposite effect through increasing IP3 and decreasing cAMP. Using available small-molecule antagonists of single EP receptors, the cyclooxygenase-2 (COX-2) inhibitor celecoxib, or a novel dual EP2/EP4 antagonist generated in this investigation, we tested which approach to block PGE2 signaling optimally restored immunologic activity in mouse and human immune cells and antitumor activity in syngeneic, spontaneous, and xenograft tumor models. We found that dual antagonism of EP2 and EP4 together significantly enhanced the activation of PGE2-suppressed mouse and human monocytes and CD8 Significance: Prostaglandin (PGE2) drives tumor progression but the pathway has not been effectively drugged. We demonstrate significantly enhanced immunologic potency and antitumor activity through blockade of EP2 and EP4 PGE2 receptor signaling together with a single molecule.
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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.