Researchers at the University of Alabama at Birmingham have identified a potential new approach to treating HPV-related cervical cancer by targeting proteins that help cancer cells survive and grow.
The findings were published in the Proceedings of the National Academy of Sciences and were led by Louise T. Chow, Ph.D., professor emeritus, and N. Sanjib Banerjee, Ph.D., assistant professor, both with the UAB Department of Biochemistry and Molecular Genetics.
High-risk human papillomavirus, or HPV, causes nearly all cervical cancers and is linked to several other cancers. While vaccines can prevent new HPV infections, they do not treat existing infections or HPV-driven cancers. Researchers are actively seeking therapies that specifically target the mechanisms that allow these cancers to persist.
In the new study, UAB scientists evaluated the effect of a novel HuR inhibitor, SRI-42127, originally developed jointly by Louis Burt Nabors, M.D., UAB and Southern Research as a novel HuR inhibitor.
The results provide strong evidence that HuR and HuB are attractive therapeutic targets.
The UAB research team from the Department of Biochemistry and Molecular Genetics found that this compound reduced levels of two RNA binding proteins, HuR and HuB, that help sustain HPV-positive cancer cells. As HuR and HuB declined, this compound reduced levels of the viral proteins E6 and E7 essential for HPV-related cancers to survive. As a result, it restored activity of p53, a critical tumor-suppressor protein often disabled in HPV-associated cancers, and slowed cancer cell growth.
Anti-cancer effects were observed in laboratory-grown cervical cancer cells, patient-derived tumor models and mouse models. Banerjee and his team found that SRI-42127 enhanced the effects of cisplatin, a commonly used chemotherapy drug for cervical cancer.
These findings reveal a promising new way to attack HPV-driven cancers by simultaneously reducing viral cancer proteins and reactivating the body’s natural tumor-suppression mechanisms. The results provide strong evidence that HuR and HuB are attractive therapeutic targets.
Chow and Banerjee indicate that additional research is needed to develop this class of inhibitors to improve bioavailable before they can be tested in clinical trials.
The research was supported in part by the Cervical Cancer Specialized Programs of Research Excellence, the National Cancer Institute and institutional support from UAB.
Chow and Banerjee are also members of the UAB O’Neal Cancer Center.