ArticleMolecular cancer therapeutics2016
Regulation of HIF1α under Hypoxia by APE1/Ref-1 Impacts CA9 Expression: Dual Targeting in Patient-Derived 3D Pancreatic Cancer Models.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 111 citations in OpenAlex.
- APE1 coordinates its disordered region and metal cofactors to drive genome surveillance.Nucleic acids research · 2026Article
- Targeting APE1 endonuclease activity impairs metastasis and enhances genotoxic therapy response in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- An APE1 Redox Inhibitor Attenuates Pathological Retinal Vascularization by Suppressing FGF2 Angiogenic Signaling.Investigative ophthalmology & visual science · 2026Article
- A phase I study targeting the APE1/Ref-1 redox signaling protein with APX3330: first clinical agent targeting APE1/Ref-1 in cancer.The oncologist · 2026Article
- Piperine alleviates retinal ischemic injury by mediating the APE1 signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Article
- Targeting APE1 endonuclease activity impairs metastasis and enhances genotoxic therapy response in pancreatic cancer.Research square · 2025Article
- Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting.NAR cancer · 2025Review
- APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism.iScience · 2025Article
- DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From DNA Repair to Redox Signaling: The Multifaceted Role of APEX1 (Apurinic/Apyrimidinic Endonuclease 1) in Cardiovascular Health and Disease.International journal of molecular sciences · 2025Review
- Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.Angiogenesis · 2025Article
- RNA-seq analysis reveals key genes associated with downregulation of APE1 in esophageal squamous cell carcinoma.Frontiers in genetics · 2025Article
- Isoliensinine exerts antitumor effects in lung adenocarcinoma by inhibiting APEX1-driven ROS production.Frontiers in pharmacology · 2025Article
- Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.Protein and peptide letters · 2025Review
- Review
- Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review).Molecular and clinical oncology · 2024Review
- APE1 inhibition enhances ferroptotic cell death and contributes to hepatocellular carcinoma therapy.Cell death and differentiation · 2024Article
- New Ref-1/APE1 targeted inhibitors demonstrating improved potency for clinical applications in multiple cancer types.Pharmacological research · 2024Article
- The APE1/REF-1 and the hallmarks of cancer.Molecular biology reports · 2024Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the United States. Aggressive treatment regimens have not changed the disease course, and the median survival has just recently reached a year. Several mechanisms are proposed to play a role in PDAC therapeutic resistance, including hypoxia, which creates a more aggressive phenotype with increased metastatic potential and impaired therapeutic efficacy. AP Endonuclease-1/Redox Effector Factor 1 (APE1/Ref-1) is a multifunctional protein possessing a DNA repair function in base excision repair and the ability to reduce oxidized transcription factors, enabling them to bind to their DNA target sequences. APE1/Ref-1 regulates several transcription factors involved in survival mechanisms, tumor growth, and hypoxia signaling. Here, we explore the mechanisms underlying PDAC cell responses to hypoxia and modulation of APE1/Ref-1 redox signaling activity, which regulates the transcriptional activation of hypoxia-inducible factor 1 alpha (HIF1α). Carbonic anhydrase IX (CA9) is regulated by HIF1α and functions as a part of the cellular response to hypoxia to regulate intracellular pH, thereby promoting cell survival. We hypothesized that modulating APE1/Ref-1 function will block activation of downstream transcription factors, STAT3 and HIF1α, interfering with the hypoxia-induced gene expression. We demonstrate APE1/Ref-1 inhibition in patient-derived and established PDAC cells results in decreased HIF1α-mediated induction of CA9. Furthermore, an ex vivo three-dimensional tumor coculture model demonstrates dramatic enhancement of APE1/Ref-1-induced cell killing upon dual targeting of APE1/Ref-1 and CA9. Both APE1/Ref-1 and CA9 are under clinical development; therefore, these studies have the potential to direct novel PDAC therapeutic treatment. Mol Cancer Ther; 15(11); 2722-32. ©2016 AACR.
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