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High Fat Exposure May Help Liver Cancer Resist Immunotherapy

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Liver cancer chronically exposed to palmitate acquires ferroptosis resistance via the downregulation of glutamine-driven hepcidin expression.DOI 10.1016j.metabol.2025.156469

Liver cancer is one of the most difficult cancers to treat. New treatments like immunotherapy have improved outcomes for some patients, but many tumors still become resistant. Scientists are now learning that certain fats in the body may play a role in this resistance.

This study looked at the effect of palmitate, a common fatty acid found in high-fat diets and in the body. Researchers discovered that when liver cancer cells are exposed to high levels of this fat for a long time, they become more resistant to a type of cell death called ferroptosis.

Ferroptosis is important because some cancer treatments depend on it to destroy tumor cells.
The researchers found that palmitate changes how cancer cells process nutrients like glutamine.

This reduces the activity of a protein called hepcidin, which controls iron levels inside cells. Lower iron levels make it harder for treatments to trigger ferroptosis, allowing cancer cells to survive.

Encouragingly, the study also found a potential way to reverse this resistance. A drug called tazemetostat restored the activity of hepcidin and made cancer cells sensitive to treatment again in laboratory models.
These findings help explain why some liver cancers respond poorly to immunotherapy. They also suggest that targeting certain metabolic pathways may improve treatment success in the future.

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Dr. Harsh J Shah
Dr Harsh Shah - GI & HPB Oncosurgeon in India
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