ArticleCancer medicine2019
Clinical candidate and genistein analogue AXP107-11 has chemoenhancing functions in pancreatic adenocarcinoma through G protein-coupled estrogen receptor signaling.
Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Pharmacodynamics and safety in relation to dose and response of plant flavonoids in treatment of cancers.Inflammopharmacology · 2025Review
- Genistein as a Chemo-modulatory Agent: Exploring its Potential in Chemosensitization and Combinatorial Therapeutic Strategies for Cancer Treatment.Current topics in medicinal chemistry · 2025Review
- Prognostic value of RRM1 and its effect on chemoresistance in pancreatic cancer.Cancer chemotherapy and pharmacology · 2024Article
- Genistein: a promising modulator of apoptosis and survival signaling in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- G Protein-Coupled Estrogen Receptor GPER: Molecular Pharmacology and Therapeutic Applications.Annual review of pharmacology and toxicology · 2023Review
- Methionine γ-Lyase-Daidzein in Combination with S-Propyl-L-cysteine Sulfoxide as a Targeted Prodrug Enzyme System for Malignant Solid Tumor Xenografts.International journal of molecular sciences · 2022Article
- Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts.International journal of molecular sciences · 2021Review
- Role of G Protein-Coupled Estrogen Receptor in Digestive System Carcinomas: A Minireview.OncoTargets and therapy · 2021Review
- Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management.Cancers · 2020Review
- Pharmacologic Activation of the G Protein-Coupled Estrogen Receptor Inhibits Pancreatic Ductal Adenocarcinoma.Cellular and molecular gastroenterology and hepatology · 2020Article
- Clinical candidate and genistein analogue AXP107-11 has chemoenhancing functions in pancreatic adenocarcinoma through G protein-coupled estrogen receptor signaling.Cancer medicine · 2019Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Despite advances in cancer therapeutics, pancreatic cancer remains difficult to treat and often develops resistance to chemotherapies. We have evaluated a bioavailable genistein analogue, AXP107-11 which has completed phase Ib clinical trial, as an approach to sensitize tumor cells to chemotherapy. Using organotypic cultures of 14 patient-derived xenografts (PDX) of pancreatic ductal adenocarcinoma, we found that addition of AXP107-11 indeed sensitized 57% of cases to gemcitabine treatment. Results were validated using PDX models in vivo. Further, RNA-Seq from responsive and unresponsive tumors proposed a 41-gene treatment-predictive signature. Functional and molecular assays were performed in cell lines and demonstrated that the effect was synergistic. Transcriptome analysis indicated activation of G-protein-coupled estrogen receptor (GPER1) as the main underlying mechanism of action, which was corroborated using GPER1-selective agonists and antagonists. GPER1 expression in pancreatic tumors was indicative of survival, and our study proposes that activation of GPER1 may constitute a new avenue for pancreatic cancer therapeutics.
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