University Hospitals Seidman Cancer Center researchers are breaking new ground with the first-ever clinical trials investigating fenofibrate, a cholesterol-lowering medication, as a treatment for HPV-positive cervical and head and neck cancers. The innovative approach comes after compelling pre-clinical results demonstrated the drug's ability to combat these cancers as effectively as traditional chemotherapy.
Promising Pre-clinical Results
Laboratory studies using cell lines and mouse models showed that fenofibrate performed comparably to cisplatin, a standard chemotherapy drug. The medication's mechanism of action centers on restoring the function of p53, a crucial tumor suppressor gene often called the "guardian of the genome," which is typically suppressed by HPV-associated oncoproteins.
"When we compare tissue samples from mice treated with fenofibrate and untreated mice, we see much greater expression of p53 in the treated mice. This drug puts the guardian of the genome back to work," explains Wendi Quinn O'Neill, MS, DDS, Research Scientist at UH Seidman Cancer Center and Assistant Professor of Otolaryngology at Case Western Reserve University School of Medicine.
Unexpected Immune System Benefits
The research revealed an additional unexpected benefit: fenofibrate appears to reprogram the tumor microenvironment, promoting immune cell infiltration into the tumor. In some cases, researchers observed only fibrous tissue and inflammatory cells where tumors had previously existed, with one instance showing complete tumor disappearance.
Clinical Trials Launch
Two Phase 1 "window" trials are now beginning at UH Seidman Cancer Center, focusing on both HPV+ cervical cancer and HPV+ head and neck squamous cell carcinoma (HNSCC) patients. These initial trials will administer fenofibrate between diagnosis and surgical treatment to verify whether the cellular changes observed in laboratory studies translate to human patients.
Potential for Targeted Therapy
Current treatments for HPV+ head and neck cancers remain identical to those used for non-HPV-related cases, despite their distinct biological characteristics. Fenofibrate's targeted approach could offer a more precise treatment method with reduced toxicity compared to conventional therapies.
"HPV+ HNSCC is really a distinct disease with a very specific driver," O'Neill notes. "In theory, we should be able to treat it with a targeted approach that specifically impacts the viral oncoproteins that drive the disease process."
Future Applications
The research team is exploring multiple potential applications for fenofibrate, including its use as a standalone treatment, in combination with cisplatin or immunotherapy, and as a preventative measure for high-risk individuals. The drug's established safety record makes it particularly promising for long-term preventive use in patients at risk of developing primary or recurrent HPV+ cancers.
