Reducing Cholesterol May Help Reduce Bladder Cancer’s Spread, Study Finds

Bladder cancer, one of the most common and challenging cancers to treat, may have a new potential vulnerability—cholesterol synthesis. A recent study has identified a protein that plays a critical role in driving bladder cancer by triggering cholesterol production. This discovery opens the door to a promising combination therapy that could suppress tumor growth and improve treatment outcomes.

The Scale of Bladder Cancer

In 2022, more than 600,000 people worldwide were diagnosed with bladder cancer, leading to over 220,000 deaths. Despite being the fourth most common cancer in men in the U.S. in 2024, it remains severely understudied compared to other cancers, such as breast and lung cancer. Current treatment options, including chemotherapy, radiation, and immune checkpoint therapy, are not always effective, highlighting the urgent need for innovative therapeutic approaches.

Targeting the PIN1 Protein

The new study, led by Tony Hunter, PhD, from the Salk Institute for Biological Studies in California, focused on a protein called PIN1. This enzyme has long been associated with cancer progression by tweaking the structure and activity of other proteins.

“PIN1 is present at high levels in many cancers, including bladder cancer,” Hunter explained. “It activates proteins in pathways that drive cancer and inactivates those that prevent excessive growth.”

The study demonstrated that PIN1 is critical for bladder cancer cells’ proliferation, survival, and ability to invade surrounding tissues. PIN1 achieves this by driving the synthesis of cholesterol, a key building block for cell membranes and essential for cell viability.

Combination Therapy: Statin and PIN1 Inhibitor

Using mouse and bladder cancer cell models, the researchers found that disrupting cholesterol synthesis in tumor cells could suppress cancer growth. A combination of two drugs proved especially effective:

• Simvastatin: A statin commonly used to lower cholesterol and treat cardiovascular diseases.
• Sulfopin: A PIN1 inhibitor that blocks the protein’s ability to stimulate cholesterol production.

“Simvastatin reduces cholesterol made by both the liver and cancer cells, while sulfopin specifically decreases cholesterol synthesis in tumor cells,” Hunter noted. “Together, this combination therapy results in much lower cholesterol levels in bladder cancer tissue, reducing tumor growth.”

Implications Beyond Bladder Cancer

PIN1 is elevated in several other cancers, including breast cancer, suggesting this approach may have broader applications. A PIN1 inhibitor combined with a statin could potentially reduce cholesterol production and tumor growth in other cancers as well.

Hunter and his team plan to investigate PIN1’s role in other cell types within bladder tumors, such as fibroblasts, which contribute to the tumor’s structural environment. They also aim to explore other products of the cholesterol biosynthesis pathway that might drive cancer progression.

Expert Insights

Jennifer Linehan, MD, a urologic oncologist at Providence Saint John’s Cancer Institute, described the study as both hopeful and groundbreaking.

“There is so much about why cancer grows that we don’t fully understand,” Linehan said. “This study highlights an innovative mechanism of treatment that targets tumor growth itself rather than just killing existing cancer cells.”

Bladder cancer treatments are particularly challenging due to the invasive nature of the disease and its tendency to recur. Advanced cases often require major surgery to remove the bladder, which significantly impacts a patient’s quality of life and can be prohibitively expensive. Linehan emphasized the importance of research focused on stopping tumor growth, reducing recurrence, and potentially providing curative solutions.

A Step Toward Better Outcomes

This study represents a significant step forward in understanding the role of cholesterol in bladder cancer and the potential of targeting PIN1 to disrupt tumor growth. While more research is needed, the findings offer hope for new, less invasive treatments that could improve survival rates and quality of life for bladder cancer patients.

By combining an existing statin with a PIN1 inhibitor, researchers may have uncovered a powerful weapon against one of the world’s most challenging cancers. This approach not only reduces tumor growth but also paves the way for similar strategies in other cancers where PIN1 and cholesterol synthesis play a role.