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Updated: Feb 10, 2026
09:25
Bioluminescent Orthotopic Model of Pancreatic Cancer Progression
Published on: June 28, 2013
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Dietary Fat Content Influences PanIN Progression and Pancreatic Cancer Development in Mice
Urvinder Kaur Sardarni1,2, Erika Y Faraoni3, Alyssa M Waller1,2
1Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Biorxiv : the Preprint Server for Biology
|February 9, 2026
Summary
Ketogenic diets (KD) significantly shorten survival in a mouse model of early pancreatic cancer, accelerating tumor progression and promoting an aggressive, invasive cancer type. This highlights the need for caution regarding KD in high-risk individuals.
Area of Science:
- Oncology
- Metabolic Research
- Cancer Biology
Background:
- Dietary macronutrients influence pancreatic cancer development.
- The effect of ketogenic diets (KD) on early pancreatic cancer is not well understood.
- Investigating lipid-rich diets' impact on Kras-driven pancreatic neoplasia is crucial.
Purpose of the Study:
- To determine how dietary lipids affect the initiation and progression of Kras-driven pancreatic cancer.
- To compare the effects of low-fat diet (LFD), high-fat diet (HFD), and KD in a mouse model.
Main Methods:
- Utilized the Ptf1aCreERT2;KrasG12V (AcinarKrasG12V) mouse model.
- Administered LFD, HFD, and KD diets.
- Assessed survival, glucose tolerance, β-hydroxybutyrate levels, tumor histology, proteomic signaling pathways (PI3K-Akt-mTOR, EGFR), and serum cytokine/chemokine profiles.
Main Results:
- KD significantly reduced survival (26 days) compared to standard diet (SD) (87 days) and LFD (57 days).
- HFD also reduced survival (35 days) versus SD.
- KD induced glucose intolerance and elevated β-hydroxybutyrate; both KD and HFD promoted aggressive PDAC with fibrosis and stromal CD39 expression, activated PI3K-Akt-mTOR/EGFR signaling, and induced pro-inflammatory/pro-angiogenic milieu.
Conclusions:
- Dietary lipid enrichment, especially KD, accelerates early pancreatic neoplasia driven by oncogenic Kras.
- These diets promote a pro-tumorigenic microenvironment.
- Caution is advised regarding KD use in individuals at high risk for pancreatic cancer.
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