ArticleMedical sciences (Basel, Switzerland)2017
Investigation of Polyamine Metabolism and Homeostasis in Pancreatic Cancers.
Article in Medical sciences (Basel, Switzerland), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 23 citations in OpenAlex.
- Inulin supplementation modulates gut microbiota derived metabolites related to brain function in children with obesity.Scientific reports · 2025Trial
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- Dual Functions of Polyamines in Shaping Host-Specific Pathogen Dynamics.Pathogens (Basel, Switzerland) · 2026Review
- Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors.International journal of biological sciences · 2025Review
- Polyamine Derived Photosensitizer: A Novel Approach for Photodynamic Therapy of Cancer.Molecules (Basel, Switzerland) · 2024Article
- Expression of ornithine decarboxylase in peripheral blood mononuclear cells from patients with pancreatic adenocarcinoma: A preliminary report.Biomedical reports · 2024Article
- Review
- Quantitative Metabolomics to Explore the Role of Plasma Polyamines in Colorectal Cancer.International journal of molecular sciences · 2022Article
- One-Carbon and Polyamine Metabolism as Cancer Therapy Targets.Biomolecules · 2022Review
- Discovery of Anthranilic Acid Derivatives as Difluoromethylornithine Adjunct Agents That Inhibit Far Upstream Element Binding Protein 1 (FUBP1) Function.Journal of medicinal chemistry · 2022Article
- 3,3'-Diindolylmethane plus Eflornithine suppress DNA Replication and Cell Cycle in Esophageal Squamous Cell CarcinomaJournal of Cancer · 2022Article
- METTL3-IGF2BP3-axis mediates the proliferation and migration of pancreatic cancer by regulating spermine synthase m6A modification.Frontiers in oncology · 2022Article
- Polyamines: Functions, Metabolism, and Role in Human Disease Management.Medical sciences (Basel, Switzerland) · 2021Review
- Lipid composition of the cancer cell membrane.Journal of bioenergetics and biomembranes · 2020Review
- Review
- Alpha-Difluoromethylornithine, an Irreversible Inhibitor of Polyamine Biosynthesis, as a Therapeutic Strategy against Hyperproliferative and Infectious Diseases.Medical sciences (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancers are currently the fourth leading cause of cancer-related death and new therapies are desperately needed. The most common pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). This report describes the development of therapies, which effectively deplete PDAC cells of their required polyamine growth factors. Of all human tissues, the pancreas has the highest level of the native polyamine spermidine. To sustain their high growth rates, PDACs have altered polyamine metabolism, which is reflected in their high intracellular polyamine levels and their upregulated import of exogenous polyamines. To understand how these cancers respond to interventions that target their specific polyamine pools, L3.6pl human pancreatic cancer cells were challenged with specific inhibitors of polyamine biosynthesis. We found that pancreatic cell lines have excess polyamine pools, which they rebalance to address deficiencies induced by inhibitors of specific steps in polyamine biosynthesis (e.g., ornithine decarboxylase (ODC), spermidine synthase (SRM), and spermine synthase (SMS)). We also discovered that combination therapies targeting ODC, SMS, and polyamine import were the most effective in reducing intracellular polyamine pools and reducing PDAC cell growth. A combination therapy containing difluoromethylornithine (DFMO, an ODC inhibitor) and a polyamine transport inhibitor (PTI) were shown to significantly deplete intracellular polyamine pools. The additional presence of an SMS inhibitor as low as 100 nM was sufficient to further potentiate the DFMO + PTI treatment.
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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.