ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Glycogen Synthase Kinase-3 Inhibition Sensitizes Pancreatic Cancer Cells to Chemotherapy by Abrogating the TopBP1/ATR-Mediated DNA Damage Response.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 48 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.
Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined With Chemotherapy, in Patients With Refractory Hematologic Malignancies or Solid Tumors
Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, as a Single Agent or Combined With Ruxolitinib, in Patients With Myelofibrosis
Phase 1 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, as a Single Agent or With Irinotecan, Irinotecan Plus Temozolomide, or With Cyclophosphamide Plus Topotecan in Pediatric Patients With Refractory Malignancies.
Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.Nature medicine · 2026Trial
- GSK3βGut · 2026Article
- Monitoring Molecular Uptake and Cancer Cells' Response by Development of Quantitative Drug Derivative Probes for Chemical Imaging.Analytical chemistry · 2025Article
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
- The Significance of the Wnt/β-Catenin Pathway and Related Proteins in Gastrointestinal Malignancies.International journal of molecular sciences · 2025Review
- Fatty acid synthase (FASN) inhibition cooperates with BH3 mimetic drugs to overcome resistance to mitochondrial apoptosis in pancreatic cancer.Neoplasia (New York, N.Y.) · 2025Article
- Revealing the multi-target compounds of Sarcandra glabra identification and inhibition of novel target genes for the treatment of pancreatic cancer.BMC complementary medicine and therapies · 2025Article
- Renal-clearable and tumor-retained nanodots overcoming metabolic reprogramming to boost mitochondrial-targeted photodynamic therapy in triple-negative breast cancer.Journal of nanobiotechnology · 2025Article
- TOPBP1 as a potential predictive biomarker for enhanced combinatorial efficacy of olaparib and AZD6738 in PDAC.Cell & bioscience · 2025Article
- Inhibition of GSK3β is synthetic lethal with FHIT loss in lung cancer by blocking homologous recombination repair.Experimental & molecular medicine · 2025Article
- Review
- Targeting stromal components in pancreatic ductal adenocarcinoma: a review.Ecancermedicalscience · 2025Review
- PARP9 drives the malignant progression of pancreatic cancer cells by regulating apoptosis, DNA damage, and multidrug efflux systems.Frontiers in cell and developmental biology · 2025Article
- Metavert synergises with standard cytotoxics in human PDAC organoids and is associated with transcriptomic signatures of therapeutic response.Translational oncology · 2024Article
- Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition.Cancer research communications · 2024Article
- MADD regulates natural killer cell degranulation through Rab27a activation.Journal of cell science · 2024Article
- The Osteocyte with SB216763-Activated Canonical Wnt Signaling Constructs a Multifunctional 4D Intelligent Osteogenic Module.Biomolecules · 2024Article
- Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Glycogen synthase kinase 3β: the nexus of chemoresistance, invasive capacity, and cancer stemness in pancreatic cancer.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- The many faceted role of glycogen synthase kinase-3 (GSK-3) in T cells and cancer immunotherapy.Journal of cancer biology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
purposePancreatic ductal adenocarcinoma (PDAC) is a predominantly fatal common malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies including PDAC.
results9-ING-41 treatment significantly increased pancreatic tumor cell killing when combined with chemotherapy. Inhibition of GSK-3 by 9-ING-41 prevented gemcitabine-induced S-phase arrest suggesting an impact on the ATR-mediated DNA damage response. Both 9-ING-41 and siRNA depletion of GSK-3 kinases impaired the activation of ATR leading to the phosphorylation and activation of Chk1. Mechanistically, depletion or knockdown of GSK-3 kinases resulted in the degradation of the ATR-interacting protein TopBP1, thus limiting the activation of ATR in response to single-strand DNA damage.
conclusionsThese data identify a previously unknown role for GSK-3 kinases in the regulation of the TopBP1/ATR/Chk1 DNA damage response pathway. The data also support the inclusion of patients with PDAC in clinical studies of 9-ING-41 alone and in combination with gemcitabine.
Indexed as
Identifiers
What OpenQuestion holds
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.