Cancer
Common cholesterol drug shows ovarian cancer promise

A common cholesterol drug could help weaken a fluid shield that helps ovarian cancer tumours survive, early lab findings suggest.
The findings do not show the drug treats ovarian cancer. But they suggest changing the environment the cancer depends on could make it more vulnerable to existing treatment.
A federally funded study at Duke University School of Medicine found that ascites, a build-up of fluid in the abdomen, may do more than cause discomfort.
Doctors can drain ascites to ease pain, improve mobility and make breathing easier, but the fluid may also help cancer cells survive and spread. It occurs in 90 per cent of people with advanced ovarian cancer.
According to the study, ascites acts as a shield, helping cancer cells evade ferroptosis, a form of cell death.
Ferroptosis is a kind of cellular rusting. It happens when iron inside a cell reacts with certain fats, causing the cell membrane to break apart.
Many metastatic cancer cells, meaning cells that float freely through the abdomen looking for new places to grow, are naturally vulnerable to this kind of damage.
“Doctors have mostly viewed ascites as a symptom rather than an active driver of disease,” said Jen-Tsan Chi, professor in the department of molecular genetics and microbiology and co-leader of the Cancer Biology Program at the Duke Cancer Institute.
“We’ve learned it gives cancer a survival advantage, which fills a major gap in understanding how ovarian cancer spreads.”
Scientists bathed cancer cell lines and patient-derived tumour cells in ascites collected from patients and watched how they responded to ferroptosis triggers.
The fluid protected cancer cells by changing how they store fats and control iron levels, effectively blocking cell death.
The protection required only trace amounts, with as little as 2 per cent immersion shielding cancer cells from destruction.
“What surprised us was how selective this effect was,” said Yasaman Setayeshpour, first author and graduate student in molecular genetics and microbiology at Duke School of Medicine.
“Ascites didn’t protect the cancer cells from other well-known types of cell death, like apoptosis or necrosis, it only blocked ferroptosis.
“To figure out why, we broke ascites down into major parts, like lipids, proteins, and small molecules, and tested what happened when each was removed.
“When we took the lipids out, the protective effect disappeared. That told us lipids are the key reason ascites helps these cancer cells survive.”
But researchers found an unexpected helper in bezafibrate, an older cholesterol drug used to lower triglycerides by altering how the body processes fats.
The cholesterol drug restored sensitivity to ferroptosis, but only when ascites was present. On its own, the drug did not trigger cell death or slow tumour growth in mice.
The drug’s impact depended on the cancer’s surroundings, in this case the fat-rich fluid bathing the tumour. Researchers found that targeting this environment, using repurposed drugs like bezafibrate, could leave cancer cells more exposed to existing cancer treatments.
Chi said the finding could have implications beyond ovarian cancer. Other cancers, including colorectal and pancreatic cancers, can also spread within the abdominal cavity.
“This work shows how much the environment around a tumour matters,” Chi said.
“Biological fluids like ascites don’t just give cancer cells a place to move. They actively help drive how cancer spreads.”
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