How overeating and metabolic stress drive NASH-related liver cancer
Official title: Role of hypernutrition and metabolic stress in non-alcoholic steatohepatitis (NASH) driven hepatocellular carcinoma (HCC)
Funded at Sanford Burnham Prebys Medical Discovery Institute · NIH-11189737 · Data updated 2026-11-12
This research looks at how excess nutrition and cell stress change liver metabolism and push NASH (fatty liver disease) toward liver cancer, with the goal of finding points to stop that process.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Sanford Burnham Prebys Medical Discovery Institute NIH-funded |
| Lab location | 1 site (La Jolla, United States) |
| Project start | September 9, 2024 |
| Project end | August 31, 2029 |
| Funding year | 2025 |
| Award (this year) | $2,302,833 |
| NIH project number | 5P01CA281819-02 |
| Project ID | NIH-11189737 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with nonalcoholic steatohepatitis (NASH) or advanced fatty liver disease who are at increased risk for hepatocellular carcinoma are the most relevant population for this research.
✕Less likely to help
Patients whose liver cancer is caused primarily by viral hepatitis, alcohol, or unrelated non-metabolic causes may not directly benefit from findings specific to NASH-driven pathways.
What this research studies
From a patient perspective, scientists are tracing how specific stress-response networks in liver cells (including NRF2, ATF6, AKT and mitochondrial factors like STARD1 and SAB) change glucose, fat, and cholesterol handling in ways that promote cancer. They will use mouse models, cell experiments, lineage tracing, and molecular analysis to find which cells switch on these pathways and what triggers that switch. The team will test what happens when individual pathway components are removed or activated to see if that slows or speeds cancer development. The overall aim is to find molecular choke points that could become targets to prevent or intercept NASH progressing to hepatocellular carcinoma.
Why it matters
Potential benefit: If successful, the work could identify drug targets or biomarkers that help prevent or block the progression from NASH to liver cancer.
How similar studies have gone: Preclinical work targeting related metabolic and stress-response pathways has shown promise in animal models, but these approaches have not yet been proven in people.
Where this research is happening
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Sanford Burnham Prebys Medical Discovery Institute
La Jolla, United States Active
Researchers
- Principal investigator: Kaufman, Randal J. — Sanford Burnham Prebys Medical Discovery Institute
- Study coordinator: Kaufman, Randal J.
Related research
Other NIH-funded projects on the same topics.
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Role of metabolic stress in NASH-related liver cancer
This grant explores how metabolic stress linked to NASH may drive liver cancer and looks for ways to interrupt that process to help patients.
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Investigating how metabolic stress contributes to liver cancer development
This study is looking at how extra weight and changes in metabolism might affect the growth of liver cancer in people with fatty liver disease, and it aims to find ways to slow down or prevent this cancer from getting worse.
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Neoadjuvant Immunotherapy Platform for Hepatocellular Carcinoma
A Johns Hopkins study will test immune-based therapy given before surgery to shrink liver cancer and help prevent recurrence.
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Using immunotherapy before surgery to improve outcomes in liver cancer
This study is looking at how giving immunotherapy before surgery can help boost the immune system's ability to fight liver cancer, and it's for patients with hepatocellular carcinoma who are preparing for surgery.
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Testing a pig model for liver cancer treatments
This study is testing a special type of pig that has been genetically modified to develop liver cancer like humans do, to help find better treatments for people with liver cancer by seeing how different genetic changes respond to targeted therapies.
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Using advanced imaging to better understand liver cancer
This study is looking at new ways to spot and treat liver cancer using advanced imaging techniques, which could help doctors understand your cancer better and find the best treatment just for you.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.