{"entity": "publication", "iuid": "e6a1e270d26b4a0ab8775ae1c8a28632", "timestamp": "2026-07-17T05:47:12.099Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e6a1e270d26b4a0ab8775ae1c8a28632.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e6a1e270d26b4a0ab8775ae1c8a28632"}}, "title": "Clinical candidate and genistein analogue AXP107-11 has chemoenhancing functions in pancreatic adenocarcinoma through G protein-coupled estrogen receptor signaling.", "authors": [{"family": "Mesmar", "given": "Fahmi", "initials": "F"}, {"family": "Dai", "given": "Bingbing", "initials": "B"}, {"family": "Ibrahim", "given": "Ahmed", "initials": "A"}, {"family": "Hases", "given": "Linnea", "initials": "L"}, {"family": "Jafferali", "given": "Mohammed Hakim", "initials": "MH"}, {"family": "Jose Augustine", "given": "Jithesh", "initials": "J"}, {"family": "DiLorenzo", "given": "Sebastian", "initials": "S"}, {"family": "Kang", "given": "Ya'an", "initials": "Y"}, {"family": "Zhao", "given": "Yang", "initials": "Y"}, {"family": "Wang", "given": "Jing", "initials": "J"}, {"family": "Kim", "given": "Michael", "initials": "M"}, {"family": "Lin", "given": "Chin-Yo", "initials": "C"}, {"family": "Berkenstam", "given": "Anders", "initials": "A"}, {"family": "Fleming", "given": "Jason", "initials": "J"}, {"family": "Williams", "given": "Cecilia", "initials": "C"}], "type": "journal article", "published": "2019-09-30", "journal": {"volume": null, "issn": "2045-7634", "issue": null, "pages": null, "title": "Cancer Med", "issn-l": "2045-7634"}, "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.", "doi": "10.1002/cam4.2581", "pmid": "31568691", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2019-12-02T17:20:33.691Z", "modified": "2024-01-16T13:48:43.797Z"}