A new research document has been published in volume 16 of Oncotarget On June 25, 2025, entitled “The accumulation of lipid droplets induced by hypoxia promotes resistance to ferroptosis in prostate cancer.”
In this study, researchers led by Shailender S. Chauhan and Noel A. Warfel from Arizona University have discovered that prostate cancer cells survive treatment by storing fat in tiny cellular compartments when oxygen levels are low.
This process makes cancer cells less vulnerable to a type of cell death known as ferroptosis.
The results provide new information on the reasons why prostate tumors often resist therapies and suggest potential strategies to improve treatment results.
This study has focused on ferroptosis, a form of programmed cell death which is based on oxidation of iron and lipids to destroy cancer cells.
The researchers tested prostate cancer cells under normal and low oxygen conditions and have found that hypoxia, or reduces oxygen levels, allowed cancer cells to build lipid droplets (LD).
These structures act as fat storage units, protecting cancer cells from oxidative damage and preventing ferroptosis from occurring.
The researchers found that this adaptation of prostate cancer cells made them less sensitive to drugs inducing ferroptosis like Erastine and RSL3, even when these drugs were combined for a stronger effect.
The team also pointed out that hypoxia had caused important changes in lipid metabolism, reducing the availability of specific fatty acids which normally promote ferroptosis.
Transcriptomic analysis revealed that hypoxia significantly reduced the expression of genes related to incorporating polyunsaturated fatty acids into phospholipids (ACSL4, LPCAT3), and parallel lipidomic analysis demonstrated that hypoxia significantly decreased the levels of the ferroptosis-prone lipid class, phosphatidylethanolamine (PE) and increased production of neutral lipid species, cholesteryl ester (ChE (22: 5)) et les triglycรฉrides (Tg (48: 1), Tg: (50: 4) et Tg (58: 4)).
This research highlights the importance of tumor microenvironment, in particular oxygen levels, to shape how cancer cells react to treatment.
By modifying their metabolism and storing lipids, prostate tumors can escape the treatments designed to trigger ferroptosis.
These results underline the need to develop new strategies targeting LD dynamics or lipid metabolism to overcome this resistance.
understand how prostate cancer (ACP) adapts to survive in hypoxic conditions offers a potential avenue for improving therapies.
For example,prevention of the accumulat
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