ArticleCellular and molecular gastroenterology and hepatology2020
Pharmacologic Activation of the G Protein-Coupled Estrogen Receptor Inhibits Pancreatic Ductal Adenocarcinoma.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 3 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 3 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review.Cancer biology & medicine · 2024Pooled it
- Predictors for Long-Term Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.Annals of surgical oncology · 2024Pooled it
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Targeting the G-protein-coupled estrogen receptor: a novel therapeutic strategy in cutaneous T-cell lymphoma.Blood neoplasia · 2026Article
- Real-World Validation of the Purity Independent Subtyping of Tumors Classifier for Informing Therapy Selection in Pancreatic Ductal Adenocarcinoma.JCO precision oncology · 2025Article
- Mitochondrial CaJournal of cellular physiology · 2025Review
- LNS-8801 as a therapeutic agent for aggressive lymphomas: ROS-induced cytotoxicity and synergy with existing therapies.Blood advances · 2025Article
- Sex- and site-specific effects of GPER-1 activation on saccharin vs cocaine preference in male and female rats.Hormones and behavior · 2025Article
- Temporal trends in cross-country inequalities of early-onset pancreatic cancer: a comprehensive analysis for the global burden of disease study 2021.Scientific reports · 2025Article
- LNS8801: An Enantiomerically Pure Agonist of the G Protein-Coupled Estrogen Receptor Suitable for Clinical Development.Cancer research communications · 2025Article
- Multi-omics insights into the molecular signature and prognosis of hypopharyngeal squamous cell carcinoma.Communications biology · 2025Article
- Estrogen Promotes the Proliferation and Migration of Endometrial Cancer Through the GPER-Mediated NOTCH Pathway.Journal of biochemical and molecular toxicology · 2025Article
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- Sex-Related Differences in Pancreatic Ductal Adenocarcinoma Progression and Response to Therapy.International journal of molecular sciences · 2024Review
- Article
- Sex Matters-Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer.Cancers · 2024Article
- Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.Nature reviews. Cancer · 2024Article
- G protein-coupled estrogen receptor 1 and collagen XVII endodomain expression in human cutaneous melanomas: can they serve as prognostic factors?Pathology oncology research : POR · 2024Article
- GPER1 signaling restricts macrophage proliferation and accumulation in human hepatocellular carcinoma.Frontiers in immunology · 2024Article
- Article
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9 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsFemale sex is associated with lower incidence and improved clinical outcomes for most cancer types including pancreatic ductal adenocarcinoma (PDAC). The mechanistic basis for this sex difference is unknown. We hypothesized that estrogen signaling may be responsible, despite the fact that PDAC lacks classic nuclear estrogen receptors.
methodsHere we used murine syngeneic tumor models and human xenografts to determine that signaling through the nonclassic estrogen receptor G protein-coupled estrogen receptor (GPER) on tumor cells inhibits PDAC.
resultsActivation of GPER with the specific, small molecule, synthetic agonist G-1 inhibited PDAC proliferation, depleted c-Myc and programmed death ligand 1 (PD-L1), and increased tumor cell immunogenicity. Systemically administered G-1 was well-tolerated in PDAC bearing mice, induced tumor regression, significantly prolonged survival, and markedly increased the efficacy of PD-1 targeted immune therapy. We detected GPER protein in a majority of spontaneous human PDAC tumors, independent of tumor stage.
conclusionsThese data, coupled with the wide tissue distribution of GPER and our previous work showing that G-1 inhibits melanoma, suggest that GPER agonists may be useful against a range of cancers that are not classically considered sex hormone responsive and that arise in tissues outside of the reproductive system.
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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.