ArticleOncotarget2015
Simultaneous targeting of 5-LOX-COX and EGFR blocks progression of pancreatic ductal adenocarcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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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
19 citing papers in PubMed, 36 citations in OpenAlex.
- Unlocking the potential: unveiling tyrphostins with Michael-reactive cyanoacrylate motif as promising inhibitors of human 5-lipoxygenase.Pflugers Archiv : European journal of physiology · 2024Article
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- Lipoxygenases at the Intersection of Infection and Carcinogenesis.International journal of molecular sciences · 2024Review
- Investigating Cox-2 and EGFR as Biomarkers in Canine Oral Squamous Cell Carcinoma: Implications for Diagnosis and Therapy.Current issues in molecular biology · 2024Article
- Triple targeting of mutant EGFRJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer.Pharmaceutics · 2023Article
- Major hurdles to the use of tyrosine kinase inhibitors in clinical prevention/interception studies: Do preclinical studies with EGFR inhibitors suggest approaches to overcome some of the limitations.Frontiers in cell and developmental biology · 2023Review
- Modulation of smoke-induced DNA and microRNA alterations in mouse lung by licofelone, a triple COX-1, COX-2 and 5-LOX inhibitor.Carcinogenesis · 2020Article
- Combination of Erlotinib and Naproxen Employing Pulsatile or Intermittent Dosing Profoundly Inhibits Urinary Bladder Cancers.Cancer prevention research (Philadelphia, Pa.) · 2020Article
- A COX-2/sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation.Theranostics · 2020Article
- Discovery and Development of a Novel mPGES-1/5-LOX Dual Inhibitor LFA-9 for Prevention and Treatment of Chronic Inflammatory Diseases.Journal of inflammation research · 2020Article
- Targeting cholecystokinin-2 receptor for pancreatic cancer chemoprevention.Molecular carcinogenesis · 2019Article
- Cancer Chemoprevention: Preclinical In Vivo Alternate Dosing Strategies to Reduce Drug Toxicities.Toxicological sciences : an official journal of the Society of Toxicology · 2019Review
- Natural Forms of Vitamin E as Effective Agents for Cancer Prevention and Therapy.Advances in nutrition (Bethesda, Md.) · 2017Review
- Article
- Mechanistic Evaluation and Translational Signature of Gemcitabine-induced Chemoresistance by Quantitative Phosphoproteomics Analysis with iTRAQ Labeling Mass Spectrometry.Scientific reports · 2017Article
- Dclk1-expressing tuft cells: critical modulators of the intestinal niche?American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Suppression of osteopontin inhibits chemically induced hepatic carcinogenesis by induction of apoptosis in mice.Oncotarget · 2016Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclooxygenase-2 (COX-2), 5-Lipoxygenase (5-LOX), and epidermal growth factor receptor (EGRF) are over-expressed in human pancreatic ductal adenocarcinoma (PDAC). Using next-generation sequencing (NGS) analysis, we show significant increase in COX-2, 5-LOX, and EGFR expression during PDAC progression. Targeting complementary pathways will achieve better treatment efficacy than a single agent high-dose strategy that could increase risk of side effects and tumor resistance. To target COX-2, 5-LOX, and EGFR simultaneously, we tested effects of licofelone (dual 5-LOX-COX inhibitor), and gefitinib (EGFR inhibitor), individually and in combination, on pancreatic intraepithelial neoplasms (PanINs) and their progression to PDAC using genetically engineered mice. Individually, licofelone (L) and gefitinib (G) significantly inhibited incidence of PDAC in male (72% L, 90% G, p < 0.0001) and female (90% L, 85% G, p < 0.0001) mice. The combination drug treatment produced complete inhibition of PDAC in both genders. Pancreata of mice receiving combination treatment showed significantly fewer Dclk1-positive cancer stem-like cells, inhibition of COX-2, 5-LOX, PCNA, EGFR and β-catenin expression (p < 0.05-0.0002), increased p21 expression. Significant changes in tumor immune responses and desmoplastic reaction was observed by NGS analysis in combination treatment (p < 0.05). In summary, early simultaneous targeting of 5-LOX-COX- and EGFR pathways may provide additive inhibitory effects leading to complete suppression of PDAC.
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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.