ArticleGastroenterology2009
Inhibition of gamma-secretase activity inhibits tumor progression in a mouse model of pancreatic ductal adenocarcinoma.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 2 of them syntheses that pooled it.
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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
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer.Cancer medicine · 2019Trial
- NOTCH pathway inactivation promotes bladder cancer progression.The Journal of clinical investigation · 2015Trial
- A phase II study of the gamma secretase inhibitor RO4929097 in patients with previously treated metastatic pancreatic adenocarcinoma.Investigational new drugs · 2014Trial
- Pancreatic Cancer: Pathogenesis and Clinical Studies.MedComm · 2025Review
- Deciphering the secrets of tumor-initiating cells in pancreatic ductal adenocarcinoma microenvironment: mechanisms and therapeutic opportunities.Frontiers in immunology · 2025Review
- FGF21 inhibits invasion and metastasis via IL-17A-Notch in pancreatic ductal adenocarcinoma.Frontiers in oncology · 2025Article
- Notch Signaling Regulates Immunosuppressive Tumor-Associated Macrophage Function in Pancreatic Cancer.Cancer immunology research · 2024Article
- DLL3 Is a Prognostic and Potentially Predictive Biomarker for Immunotherapy Linked to PD/PD-L Axis and NOTCH1 in Pancreatic Cancer.Biomedicines · 2023Article
- Pancreatic cancer stemness: dynamic status in malignant progression.Journal of experimental & clinical cancer research : CR · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- CODA: quantitative 3D reconstruction of large tissues at cellular resolution.Nature methods · 2022Article
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- Significant Roles of NotchMolecules (Basel, Switzerland) · 2022Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- SOX9 modulates cancer biomarker and cilia genes in pancreatic cancer.Human molecular genetics · 2021Article
- Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and L-fringe in Pancreatic Cancers.Molecules (Basel, Switzerland) · 2021Article
- More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment.The oncologist · 2021Article
- Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer.Frontiers in cell and developmental biology · 2021Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe Notch signaling pathway is required for the expansion of undifferentiated pancreatic progenitor cells during embryonic development and has been implicated in the progression of pancreatic ductal adenocarcinoma (PDAC). The interaction of Notch ligands with their receptors promotes a gamma-secretase-dependent cleavage of the Notch receptor and release of the Notch intracellular domain, which translocates to the nucleus and activates transcription. We investigated the role of this pathway in PDAC progression.
methodsWe tested the effects of a gamma-secretase inhibitor (GSI) that blocks Notch signaling in PDAC cell lines and a genetically engineered mouse model of PDAC (Kras p53 L/+ mice).
resultsNotch signaling was activated in PDAC precursors and advanced tumors. The GSI inhibited the growth of premalignant pancreatic duct-derived cells in a Notch-dependent manner. Additionally, in a panel of over 400 human solid tumor-derived cell lines, PDAC cells, as a group, were more sensitive to the GSI than any other tumor type. Finally, the GSI completely inhibited tumor development in the genetically engineered model of invasive PDAC (P < .005, chi2 test; compared with mice exposed to vehicle).
conclusionsThese results suggest that Notch signaling is required for PDAC progression. Pharmacologic targeting of this pathway offers therapeutic potential in this treatment-refractory malignancy.
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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.