Doris Mangiaracina Benbrook, Ph.D. and colleague.

What if the women at high risk for getting cervical cancer need never fear getting that cancer? A researcher at the Stephenson Cancer Center at the University of Oklahoma believes she may have found a way; and with a new $2.2 million grant from the National Institutes of Health, she and her team aim to prove it.
Cervical cancer affects about 528,000 women worldwide and is the second leading cause of cancer-related deaths among women. It’s a cancer that starts with changes in cells of the cervix that are abnormal but not cancerous. The changes, also known as cervical dysplasia, often are triggered by the human papillomavirus, the most common sexually transmitted infection.
According to the Centers for Disease Control and Prevention, about 79 million people are currently infected with HPV, and some 14 million are newly infected each year in the United States.
Doris Mangiaracina Benbrook, Ph.D., believes she and colleague researchers have developed a compound that can successfully stop cervical cancer before it even starts in those infected with HPV.
“We developed a non-toxic, orally-bioavailable, small molecule drug called OK-1 and aim to demonstrate its usefulness for treatment of cervical dysplasia and cancer,” Benbrook said. “In a new clinical trial, we aim to see how the drug counteracts the effects of the human papillomavirus.”
Benbrook explained that cancer is not normal evolution for the virus but rather a rare accident. In the natural life cycle of the virus, certain proteins cause the disposal of two key proteins in normal cells of the cervix. Those proteins function as tumor suppressors, meaning they are responsible for regulating cellular DNA replication as well as whether a cell survives or dies, a critical component of the body’s ability to prevent a cell from becoming cancerous.
“We’ve shown in our studies that OK-1 counteracts the effects of the virus proteins on the tumor suppressors, thereby preventing cancer, Benbrook said. “This grant will allow us to test this further in more experimental models and in a clinical trial.”
In addition to delivering the compound in capsule form, she said the team is developing a vaginal suppository formulation to be used in the clinical trial.
“In the United States, a third of the women diagnosed with cervical cancer will die from their disease. Currently, cervical cancer is treated with therapeutic adjuvants like chemotherapy, which have improved survival but are highly toxic and often negatively impact quality of life. So there’s a very real need for the development of effective new treatments, which will improve efficacy or lower treatment-related toxicity or ideally both.”
Benbrook and her team are collaborating with fellow researchers at the Stephenson Cancer Center, the OU Health Sciences Center and MD Anderson Cancer Center.
“Dr. Benbrook’s grant is a testimony to the power of team science being done at the Stephenson Cancer Center, bringing researchers together from a variety of disciplines creating a new drug that holds the promise of helping thousands of women each year just in Oklahoma,” said Robert Mannel, M.D., director of the Stephenson Cancer Center.
Other researchers from the University of Oklahoma Health Sciences Center who will be involved in this work include: Lucilla Garcia-Contreras, Ph.D.; Altaf Mohammed, Ph.D.; C.V. Rao, Ph.D.; Sukyung (Sue) Woo, Ph.D.; Yan (Daniel) Zhao, Ph.D. and Rosemary Zuna, Ph.D.
Last year, Benbrook received a $3 million grant from the NIH for the first-in-human clinical trial of OK-1 in women with ovarian cancer. The cervical cancer research is funded by NIH grant R01 CA200126