ArticleCancer prevention research (Philadelphia, Pa.)2014
Eflornithine (DFMO) prevents progression of pancreatic cancer by modulating ornithine decarboxylase signaling.
Article in Cancer prevention research (Philadelphia, Pa.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 58 citations in OpenAlex.
- Ototoxicity of Long-Term α-Difluoromethylornithine for Skin Cancer Prevention.The Laryngoscope · 2023Trial
- A new hope: Clinical advances in targeted therapies for pediatric diffuse midline glioma.Neuro-oncology advances · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- ODC-Driven Polyamines Synthesis Sustains the Self-Renewal of Glioblastoma Stem Cells and Drives Tumor Aggressiveness.Cancer science · 2025Article
- The MUC1-HIF-1α signaling axis regulates pancreatic cancer pathogenesis through polyamine metabolism remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A newAmino acids · 2023Article
- One-Carbon and Polyamine Metabolism as Cancer Therapy Targets.Biomolecules · 2022Review
- Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach.Journal of microbiology and biotechnology · 2022Article
- 3,3'-Diindolylmethane plus Eflornithine suppress DNA Replication and Cell Cycle in Esophageal Squamous Cell CarcinomaJournal of Cancer · 2022Article
- The Role of Feedback Loops in Targeted Therapy for Pancreatic Cancer.Frontiers in oncology · 2022Review
- Article
- DFMO Improves Survival and Increases Immune Cell Infiltration in Association with MYC Downregulation in the Pancreatic Tumor Microenvironment.International journal of molecular sciences · 2021Article
- The First Insight Into the Supramolecular System ofFrontiers in chemistry · 2021Article
- S-adenosylmethionine: A metabolite critical to the regulation of autophagy.Cell proliferation · 2020Review
- Article
- Review
- Targeting cholecystokinin-2 receptor for pancreatic cancer chemoprevention.Molecular carcinogenesis · 2019Article
- Wnt/β-Catenin Signaling: The Culprit in Pancreatic Carcinogenesis and Therapeutic Resistance.International journal of molecular sciences · 2019Review
- PGC1α Inhibits Polyamine Synthesis to Suppress Prostate Cancer Aggressiveness.Cancer research · 2019Article
- Targeting metabolic vulnerabilities of cancer: Small molecule inhibitors in clinic.Cancer reports (Hoboken, N.J.) · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Ornithine decarboxylase (ODC) is the key rate-limiting enzyme in the polyamine synthesis pathway and it is overexpressed in a variety of cancers. We found that polyamine synthesis and modulation of ODC signaling occurs at early stages of pancreatic precursor lesions and increases as the tumor progresses in Kras-activated p48(Cre/+)-LSL-Kras(G12D/+) mice. Interest in use of the ODC inhibitor eflornithine (DFMO) as a cancer chemopreventive agent has increased in recent years since ODC was shown to be transactivated by the c-myc oncogene and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. We tested the effects of DFMO on pancreatic intraepithelial neoplasias (PanIN) and their progression to pancreatic ductal adenocarcinoma (PDAC) in genetically engineered Kras mice. The Kras(G12D/+) mice fed DFMO at 0.1% and 0.2% in the diet showed a significant inhibition (P < 0.0001) of PDAC incidence compared with mice fed control diet. Pancreatic tumor weights were decreased by 31% to 43% (P < 0.03-0.001) with both doses of DFMO. DFMO at 0.1% and 0.2% caused a significant suppression (27% and 31%; P < 0.02-0.004) of PanIN 3 lesions (carcinoma in situ). DFMO-treated pancreas exhibited modulated ODC pathway components along with decreased proliferation and increased expression of p21/p27 as compared with pancreatic tissues derived from mice fed control diet. In summary, our preclinical data indicate that DFMO has potential for chemoprevention of pancreatic cancer and should be evaluated in other PDAC models and in combination with other drugs in anticipation of future clinical trials.
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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.