A groundbreaking study from the University Hospitals Seidman Cancer Center has unveiled the potential of fenofibrate, a cholesterol-lowering medication, as an innovative treatment for cancers associated with human papillomavirus (HPV). Preclinical research indicates that fenofibrate can restore the function of the p53 tumor suppressor gene, often called the "guardian of the genome," which is impaired by HPV oncoproteins. The drug's effectiveness rivals that of cisplatin, a traditional chemotherapy agent, suggesting a less toxic alternative for patients. Researchers are now initiating clinical trials to evaluate fenofibrate's impact on HPV-positive cervical and head and neck cancers.

Fenofibrate Reactivates the Tumor Suppressor Gene p53

Preclinical studies have demonstrated that fenofibrate can counteract the detrimental effects of HPV oncoproteins, thereby restoring the functionality of the p53 gene. This restoration significantly enhances the body's natural defenses against cancer. The researchers observed increased expression of p53 in treated mice compared to untreated ones, indicating a promising therapeutic avenue.

In-depth analysis revealed that fenofibrate not only reactivates p53 but also alters the tumor microenvironment. Mice treated with fenofibrate exhibited immune cell infiltration into the tumor site, suggesting enhanced immune response. In some cases, tumors were almost entirely replaced by fibrous tissue and inflammatory cells, pointing to a robust anti-tumor effect. This finding underscores the drug's potential to boost the host's immune system, effectively turning the tables on cancer progression.

Clinical Trials to Validate Fenofibrate’s Potential

To translate these preclinical successes into clinical benefits, two Phase 1 trials are being launched at the University Hospitals Seidman Cancer Center. These trials will involve patients with HPV-positive cervical cancer and head and neck squamous cell carcinoma (HNSCC). Participants will receive fenofibrate during the period between diagnosis and surgery, allowing researchers to analyze changes in cellular signaling pathways. Although these initial trials do not test therapeutic doses, they aim to establish whether the laboratory findings hold true in human subjects.

If successful, fenofibrate could offer a more targeted and less toxic approach to treating HPV-related cancers. Unlike current treatments that apply equally to all head and neck cancers regardless of HPV status, fenofibrate targets the specific viral oncoproteins driving HPV-positive cancers. This targeted therapy could reduce toxicity and improve patient outcomes. Additionally, given its excellent safety profile, fenofibrate holds promise as a preventive agent for individuals at high risk of developing primary or recurrent HPV-positive cancers. The Kathy and Les Coleman Clinical Trials Center at UH Seidman Cancer Center offers over 400 clinical trials, providing ample opportunities for further exploration of this novel treatment modality.