Cholesterol-lowering drugs may help slow bladder cancer growth

CALIFORNIA: In a groundbreaking study published in Cancer Discovery, researchers have identified a key protein that drives bladder cancer growth by promoting cholesterol synthesis, opening new possibilities for targeted therapies.

The study, led by Dr. Tony Hunter from the Salk Institute for Biological Studies, focuses on the protein PIN1, which plays a crucial role in altering protein structures and regulating cancer progression. Elevated levels of PIN1 have been linked to various cancers, including breast and bladder cancer.

Using mouse and cancer cell models, the research team demonstrated that PIN1 stimulates bladder cancer by triggering the production of cholesterol — a fundamental building block for cell membranes. Cholesterol biosynthesis within tumor cells enhances their growth, migration, and ability to invade surrounding tissue.

To counteract this mechanism, the researchers combined two drugs: a statin, commonly used for lowering cholesterol in humans, and a PIN1 inhibitor called sulfopin. The combination disrupted cholesterol production in cancer cells, reducing tumor growth significantly.

“Statins block liver cholesterol synthesis, while sulfopin targets cholesterol production directly in cancer cells,” Dr. Hunter explained. “Together, they effectively lower cholesterol in bladder cancer tissue, helping to suppress tumor development.”

Bladder cancer remains one of the most common cancers in men, with over 600,000 cases diagnosed globally in 2022. Despite advances in immunotherapy, the disease often requires invasive surgery and frequent follow-ups, making it one of the costliest cancers to treat.

Commenting on the study, Dr. Jennifer Linehan, a urologic oncology specialist, emphasized the significance of exploring growth-suppressing treatments. “This is a promising approach because most therapies focus on destroying existing cancer cells. Targeting cholesterol synthesis to inhibit growth offers a novel and hopeful pathway,” she noted.

The study’s findings may also have broader implications, as PIN1-driven cholesterol production could play a role in other cancers. Researchers are planning further investigations to explore additional PIN1 targets and potential combination therapies.