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This study aims to investigate the mechanisms behind ferroptosis resistance in pancreatic cancer, focusing on the role of HIF-2.

April 4, 2026Molecular CellOpen Access

The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer

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This study aims to investigate the mechanisms behind ferroptosis resistance in pancreatic cancer, focusing on the role of HIF-2.
Examined the effects of pancreatic tumor interstitial fluid and hypoxia on ferroptosis resistance.
Analyzed the expression of cystine transporter and transsulfuration pathway enzymes.
Assessed the role of HIF-2 in regulating intracellular cysteine levels and glutathione production.
HIF-2 was found to significantly protect pancreatic cancer cells from ferroptosis.
Increased expression of the system Xc− cystine transporter and cysteine production were linked to HIF-2 activity.
HIF-2 also promoted mitophagy and suppressed reactive oxygen species generation, enhancing cell survival.

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This research reveals HIF-2's critical role in ferroptosis resistance in pancreatic cancer, suggesting new therapeutic targets.

Hubbi et al. (2026) studied this question.

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