In 2022, over 600,000 people worldwide were diagnosed with bladder cancer, and more than 220,000 succumbed to the disease. Despite its prevalence, bladder cancer remains underrepresented in major cancer discussions and research.

“In 2024, bladder cancer was the fourth most common cancer diagnosed in men in the U.S., and the eighth leading cause of cancer-related deaths. Yet, it is almost never mentioned as one of the major cancers and is severely understudied,” noted Tony Hunter, PhD, American Cancer Society Professor and Renato Dulbecco Chair at the Salk Institute for Biological Studies in California.

Dr. Hunter also highlighted the limitations of current treatment options. While immune checkpoint therapy has emerged as a treatment, chemotherapy, radiation, and Bacillus Calmette-Guerin (BCG) therapy remain the most widely used approaches. “Clearly, there is an unmet need for new therapeutic strategies for bladder cancer,” he said.

New Study Uncovers a Key Protein Driving Bladder Cancer

Dr. Hunter is the senior author of a groundbreaking study recently published in Cancer Discovery. The research identifies a protein, PIN1, as a driver of bladder cancer through its role in cholesterol synthesis. Using mouse and cancer cell models, the study reveals that targeting PIN1 disrupts this pathway, suppressing cancer cell growth and tumor progression.

The Role of PIN1 in Cancer Progression

PIN1 is an enzyme that modifies protein structures, impacting their activity. Dr. Hunter explained, “PIN1 alters proteins after they’ve been tagged with a phosphate group, affecting their activity either positively or negatively. It’s present in all organisms with cell nuclei, underscoring its importance.”

In bladder cancer, PIN1 facilitates cancer cell proliferation, prevents apoptosis (programmed cell death), and promotes tumor migration and invasion. “Our work shows that PIN1 is essential for tumor cells to grow and survive,” Dr. Hunter emphasized.

Combining Therapies to Target Cholesterol Synthesis

The study also explored a promising combination therapy using the cholesterol-lowering drug simvastatin and a PIN1 inhibitor called sulfopin. Researchers found that this dual approach significantly reduced cholesterol levels in bladder cancer tissues, curbing tumor growth.

“Simvastatin blocks cholesterol synthesis in the liver and in cancer cells, while sulfopin reduces cholesterol production within tumor cells. Together, this results in much lower cholesterol levels in bladder cancer tissues, hindering tumor progression,” Dr. Hunter explained.

Potential Applications Beyond Bladder Cancer

Given the elevated levels of PIN1 in other cancers, the study raises the possibility of applying similar treatments to other malignancies. “A PIN1 inhibitor combined with a statin could be a viable option for other cancers where PIN1 drives cholesterol production,” Dr. Hunter said.

Future research will investigate PIN1’s roles in other cell types involved in bladder cancer and identify additional targets within the cholesterol biosynthesis pathway.

Expert Opinions: A Step Forward in Cancer Treatment

Dr. Jennifer Linehan, a board-certified urologist and associate professor at Providence Saint John’s Cancer Institute in Santa Monica, CA, praised the study as a hopeful advancement. “There is so much we don’t understand about why cancer grows and becomes invasive. This study offers a glimpse into one of the mechanisms at play,” she told Medical News Today.

Dr. Linehan highlighted the challenges of treating bladder cancer, particularly invasive forms that often require bladder removal. “This is a life-changing surgery with significant physiological impacts. Recurrent, non-invasive bladder cancer also places a heavy burden on patients due to frequent treatments and monitoring,” she said.

A Promising Path Ahead

The study’s findings open new avenues for treating bladder cancer by focusing on the underlying mechanisms of tumor growth. “Current treatments primarily aim to eliminate existing cancer cells,” Dr. Linehan noted. “This research introduces a novel approach to stunting tumor growth by targeting the cholesterol synthesis pathway. It’s a promising direction that deserves further exploration.”

As researchers continue to delve deeper into the role of PIN1 and its broader implications, the study represents a significant step toward understanding and combating bladder cancer.