Cholesterol-lowering drugs already prescribed to millions of adults could one day help slow the progression of ovarian cancer, new research suggests.
Ovarian Cancer in the UK
Ovarian cancer is the sixth most common cancer among women in the UK, affecting around 7,600 each year. Approximately 4,000 of these women will die from the disease, with cancer risk increasing every time a woman ovulates. Yet the symptoms of ovarian cancer, such as bloating, are not always obvious, meaning it is often diagnosed late when it is harder to treat.
The Role of Ascites
One of the most common red-flag signs is bloating, caused by a build-up of fluid in the abdomen known as ascites. Ascites occurs in 90 per cent of women with advanced ovarian cancer, causing bloating, nausea, reduced appetite, breathlessness, and fatigue. Until now, experts have primarily viewed the build-up of fluid as a symptom, rather than an active driver of disease. But now US scientists believe this fluid may help cancer cells survive and spread, and a decades-old cholesterol drug may be able to disrupt that protection.
'We've learned it gives cancer a survival advantage, which fills a major gap in understanding how ovarian cancer spreads,' said study lead author Professor Jen-Tsan Chi.
Bezafibrate and Cancer Cell Survival
The findings do not show that the drug, called bezafibrate, which works by altering how the body processes fat, can treat ovarian cancer. But they suggest that making it harder for cancer cells to survive could make tumours more responsive to existing treatments.
The study, published in the journal Nature Communications, found that the fluid helps cancer cells avoid a type of cell death called ferroptosis. This happens when the iron inside a cell reacts with fats, causing the cell membrane to 'rust' and break apart. Metastatic cancer cells, which break away from the original tumour and spread elsewhere in the body, are normally vulnerable to this kind of damage.
Laboratory Findings
Researchers from the Duke Cancer Institute immersed tumour cells in fluid collected from patients to see how they responded to cell-death triggers. They found the fluid shielded cancer cells from death by altering the way they processed fats and iron. In patients with advanced ovarian cancer, these cells are entirely enveloped by the fluid. But lab studies showed even two per cent coverage was enough to protect them.
Interestingly, the fluid only appeared to protect cancer cells from ferroptosis; it did not protect against other well-known types of cell death. '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,' explained study first author Yasaman Setayeshpour, an expert in microbiology. 'When we took the lipids (fats) out, the protective effect disappeared. That told us lipids are the key reason ascites helps these cancer cells survive.'
Cholesterol-Lowering Drugs as a Potential Treatment
To remove lipids, a type of fat found in every cell in the body, the researchers tested a number of cholesterol-lowering drugs. Cholesterol is a fatty substance naturally produced by the body that plays a vital role in keeping us healthy. But problems arise when levels of so-called 'bad' cholesterol become too high. Over time, excess low-density lipoprotein (LDL) can build up inside blood vessels, forming fatty deposits that restrict blood flow and raise the risk of heart attack, stroke, and dementia.
Cholesterol-lowering medications work by blocking an enzyme the liver needs to make cholesterol, encouraging it to remove cholesterol from the blood. Now researchers believe this fatty environment around tumours may also help protect cancer cells. When less fat was present in the fluid, as a result of cholesterol-lowering drugs, cancer cells died more readily.
The researchers concluded that targeting this typically fat-rich environment with repurposed cholesterol drugs could leave cancer cells more vulnerable to existing cancer treatments. Professor Chi added: 'This work shows how much the environment around a tumour matters. Biological fluids like ascites don't just give cancer cells a place to move. They actively help drive how cancer spreads.'
Current Treatment and Symptoms
Doctors can already drain fluid from the abdomen using a small tube to relieve symptoms, but this is not currently used to slow the progression of the disease. Other symptoms of ovarian cancer include pain or tenderness in the abdomen or pelvis, indigestion, a change in bowel habits, back pain, fatigue, abnormal bleeding, and unexplained weight loss.
