New Research Suggests Cholesterol Drugs Could Help Slow Ovarian Cancer Progression
Ovarian cancer is a significant health concern, particularly for women in the UK, where it ranks as the sixth most common cancer. Each year, approximately 7,600 women are diagnosed with the condition, and around 4,000 of them will lose their lives. The risk of developing ovarian cancer increases with each ovulation, making it a complex and challenging disease to manage.
One of the primary challenges in treating ovarian cancer is its late diagnosis. Symptoms such as bloating can be subtle and often go unnoticed, leading to delayed detection when the cancer is more difficult to treat. Bloating, in particular, is a red-flag sign caused by a build-up of fluid in the abdomen known as ascites. This condition affects 90% of women with advanced ovarian cancer and can lead to nausea, reduced appetite, breathlessness, and fatigue.
For many years, medical professionals have viewed the accumulation of fluid as merely a symptom of the disease. However, recent research suggests that this fluid may play a more active role in the progression of ovarian cancer. Scientists from the United States believe that the fluid could help cancer cells survive and spread, and a decades-old cholesterol-lowering drug might offer a solution.
The study, led by Professor Jen-Tsan Chi, found that the fluid surrounding tumours provides cancer cells with a survival advantage. This discovery fills a critical gap in understanding how ovarian cancer spreads. While the drug, called bezafibrate, does not directly treat ovarian cancer, it may make tumours more responsive to existing treatments by disrupting the protective environment around cancer cells.
The research, published in Nature Communications, revealed that the fluid helps cancer cells avoid a type of cell death known as ferroptosis. This process occurs when iron inside a cell reacts with fats, causing the cell membrane to ‘rust’ and break apart. Metastatic cancer cells, which spread to other parts of the body, are typically vulnerable to this form of damage. However, the fluid in ascites appears to shield these cells from ferroptosis.
To investigate this phenomenon, researchers at the Duke Cancer Institute immersed tumour cells in fluid collected from patients and observed their response to cell-death triggers. They discovered that the fluid altered the way cancer cells processed fats and iron, protecting them from death. Even minimal coverage—just 2%—was enough to provide protection in laboratory studies.
Interestingly, the fluid only protected cancer cells from ferroptosis and not from other types of cell death. To understand why, the study’s first author, Yasaman Setayeshpour, broke down ascites into its major components—lipids, proteins, and small molecules—and tested the effects of removing each part. When lipids were removed, the protective effect disappeared, indicating that they are the key factor in helping cancer cells survive.
Lipids, a type of fat found in every cell in the body, are crucial for cellular function. However, excessive levels of certain fats, such as low-density lipoprotein (LDL), can lead to health problems like heart disease and stroke. Cholesterol-lowering medications work by blocking an enzyme the liver needs to produce cholesterol, encouraging the body to remove it from the blood.
The researchers believe that the fatty environment around tumours may also contribute to the protection of cancer cells. When less fat was present in the fluid, as a result of cholesterol-lowering drugs, cancer cells died more readily. Targeting this fat-rich environment with repurposed cholesterol drugs could leave cancer cells more vulnerable to existing treatments.
Professor Chi emphasized the importance of the tumour’s surrounding environment. “Biological fluids like ascites don’t just give cancer cells a place to move. They actively help drive how cancer spreads,” he said.
In addition to bloating, other symptoms of ovarian cancer include pain or tenderness in the abdomen or pelvis, indigestion, changes in bowel habits, back pain, fatigue, abnormal bleeding, and unexplained weight loss. While doctors currently drain fluid from the abdomen to relieve symptoms, this approach is not used to slow the progression of the disease.
Further research is needed to explore the full potential of cholesterol-lowering drugs in managing ovarian cancer. However, the findings suggest a promising new avenue for treatment that could improve outcomes for patients.
