New Drug Shows Promise in Treating Head and Neck Cancer Caused by HPV
A new drug shows great promise in melting away the cancer cells in head and neck tumors caused by human papillomavirus (HPV).
The drug, which reactivates the anti-cancer p53 gene, was developed under the leadership of Quintin Pan, PhD, a professor in the Otolaryngology Department at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James).
Pan’s drug, OHM1, will soon begin clinical trials and could revolutionize the treatment of head and neck cancers caused by HPV. The drug could also be used to treat cervical and anal cancers, said Ted Teknos, MD, Chairman of the Department of Otolaryngology – Head and Neck Surgery at the OSUCCC – James, and Pan’s mentor.
This groundbreaking research comes from a scientist who, in high school and even into his early college years, had limited interest in biology, oncology or research. It took a life-changing event that impacted the entire Pan family to change his career path.
His mother, Jenny, was diagnosed with cervical cancer, a cancer associated with HPV. “It was stage-4 when she was diagnosed and it was a rough go for the entire family,” Pan said, adding his mom passed away about 18 months after her diagnosis.
This changed everything.
“I decided to do something that was more research-oriented based on my mom’s experiences,” Pan said. “It was 25 years ago, and the treatment options were so limited: Standard chemo – very toxic drugs. I wanted to find new therapies for cancer.”
Pan went on to earn a PhD in pharmacology from the University of Michigan and began his career as a researcher. He initially delved into how Vitamin D can reduce the risk of cancer, and then began to work with Sofia Merajver, MD, PhD, a professor of Internal Medicine at the University of Michigan, on the connection between excess copper and breast cancer — and the effectiveness of the drug tetrathiomolybdate.
“My role was to understand how tetrathiomolybdate works on the molecular level,” Pan said, adding he also dove deep into the exploration of Protein Kinase C (PKC), “that was found to be elevated in breast cancer and responsible for metastasis.”
At the same time, Dr. Teknos was Division Chief of Michigan’s Head & Neck Oncology Division.
“Dr. Teknos talked to me about head and neck cancer and said that not a lot of people were working in this area and that I should consider looking at PKC in relation to head and neck cancer.”
“Quintin was brilliant at what he was doing, and the work he was doing was transferable to all types of cancer,” Dr. Teknos said.
The two began working together, and when Dr. Teknos was recruited to come to the OSUCCC – James in 2008, he in turn recruited Pan.
“You want people who are brilliant and hungry and humble and passionate and he fit all those qualities,” said Dr. Teknos, who also recruited and brought with him from Michigan: Pawan Kumar, PhD, Bhavna Kumar, MS, and Mozaffar Islam, PhD. Teknos has since added Edmund Mroz, PhD, Jas Lang, PhD and James Rocco, MD, PhD to the Department of Otolaryngology. This collection of talented collaborators combined to create one of the top clinical and research head and neck cancer centers in the world.
About 80 million people in the United States are infected with HPV, according to the Centers for Disease Control and Prevention. It is typically spread through sexual contact and can lie dormant in the body for years, or forever, but can also spring to life and cause genital warts in men and women, cervical cancer in women, and head and neck cancer in men and women.
The American Cancer Society estimates there will be about 50,000 people diagnosed with head and neck cancer in the United States this year, and about 10,000 deaths.
Pan’s research looked at p300, which is an important protein. It regulates and the body’s p53 protein and alerts it that something is wrong. When alerted to the danger, the p53 can then activate the suicide “switch” that kills cancer cells before they become malignant and spread.
However, when the HPV E6 gene binds to the p300, it turns off the cell-killing switch. The cancer cells grow out of control and create a subset of head and neck cancers that predominately occur in the oropharynx (the middle part of the throat behind the mouth).
Using computer modeling, Pan pinpointed the spot where the HPV E6 binds to the p300. “We narrowed it down to a few hot spots and then designed molecules based on these hot spots,” Pan said, adding the second generation of the cancer-fighting molecule, OHM1, has been licensed to Inthera Bioscience, a Swiss company that will invest $10 million in the development of the drug.
“They have an aggressive timeline and clinical trials could start in early 2018,” Pan said.
Pan’s drug could have widespread application, Dr. Teknos said.
“There’s no question HPV became a huge health issue in the 1950s and 1960s due to the sexual revolution,” Dr. Teknos said, adding it has increased the incidence of head and neck, cervical and anal cancers. “It’s become a world-health issue.”
If OHM1 is approved by the FDA for the treatment of head and neck cancers, it could then be used to treat cervical and anal cancers. “It could be effective for any HPV-driven cancer,” Pan said.
And this brings us back to Jenny Pan.
Pan says developing this new drug “has brought me full circle, back to the experiences of dealing with my mother’s battle, which is something we still deal with on a daily basis. With cancer, having additional drugs, additional treatments, is so important … and will help future families.”
Pan requested his photo not be used with this blog post. The photo used here is of his mentor, Dr. Teknos.