ArticleInternational journal of oncology2014
Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine.
Article in International journal of oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- Hypoxic Tumor Microenvironment Targeting: Opportunities and Challenges for Pancreatic Cancer Immunotherapy.International journal of molecular sciences · 2026Review
- PIK75 effectively reverses PI3K‒AKT activation caused by palbociclib resistance and synergistically inhibits the progression of esophageal squamous cell carcinoma.Scientific reports · 2025Article
- JAK2 Inhibition Augments the Anti-Proliferation Effects by AKT and MEK Inhibition in Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- Therapeutic implication of oxidative stress-induced growth inhibitor 1 (OSGIN1) in cancer.Oncogene · 2025Review
- 4-Methyl-N-(Piperidin-1-Ylmethylene) Benzenesulfonamide (PMSA) Promotes Ferroptosis of Tumor Cells by Targeting theIranian journal of public health · 2024Article
- Precision Targeting Strategies in Pancreatic Cancer: The Role of Tumor Microenvironment.Cancers · 2024Review
- The Role of Nrf2 in the Regulation of Mitochondrial Function and Ferroptosis in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers.OncoTargets and therapy · 2024Review
- NFR2/ABC transporter axis in drug resistance of breast cancer cells.Molecular biology reports · 2023Review
- The RSL3 Induction ofCancers · 2022Article
- Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Brucein D augments the chemosensitivity of gemcitabine in pancreatic cancer via inhibiting the Nrf2 pathway.Journal of experimental & clinical cancer research : CR · 2022Article
- Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response.Molecules (Basel, Switzerland) · 2022Review
- Role of Nrf2 in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Ferroptosis: At the Crossroad of Gemcitabine Resistance and Tumorigenesis in Pancreatic Cancer.International journal of molecular sciences · 2021Review
- Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma.Cancers · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
We describe the potential benefit of PIK-75 in combination of gemcitabine to treat pancreatic cancer in a preclinical mouse model. The effect of PIK-75 on the level and activity of NRF2 was characterized using various assays including reporter gene, quantitative PCR, DNA-binding and western blot analyses. Additionally, the combinatorial effect of PIK-75 and gemcitabine was evaluated in human pancreatic cancer cell lines and a xenograft model. PIK-75 reduced NRF2 protein levels and activity to regulate its target gene expression through proteasome-mediated degradation of NRF2 in human pancreatic cancer cell lines. PIK-75 also reduced the gemcitabine-induced NRF2 levels and the expression of its downstream target MRP5. Co-treatment of PIK-75 augmented the antitumor effect of gemcitabine both in vitro and in vivo. Our present study provides a strong mechanistic rationale to evaluate NRF2 targeting agents in combination with gemcitabine to treat pancreatic cancers.
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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.