Dr. Susan Mallery, a professor in the College of Dentistry at The Ohio State University and Oral Pathology Consultant at the Ohio State University and James Cancer hospitals, has dedicated her nearly 30-year career to studying new strategies to preventing oral cancer. Oral cancer is currently responsible for more than 7,000 deaths each year, and has a particularly high mortality rate. Treatment relies on excising cells before they turn cancerous, but as many as one-third of all patients will experience a recurrence within a year.
"While not all oral lesions progress to cancer, we cannot accurately predict which will be the 'bad actors.' This often results in multiple surgeries and high anxiety in both our patients and clinicians," says Mallery.
Since 2003, Mallery has been investigating a variety of agents ranging from anti-angiogenesis drugs to natural products, to identify new therapeutics that can suppress the conversion of pre-cancerous to cancerous cells. Her first breakthrough was the creation of an oral gel based on anthocyanins, powerful antioxidants found in black raspberries. Study results showed that the gel, when applied to the mouth, would suppress genes associated with functions that allow cancerous cells to grow, thus diminishing the risk for recurring lesions.
Mallery next turned her attention to identifying alternatives to the surgical removal of pre-cancerous lesions. Mallery thought she might have good possibilities with fenretinide, a decades-old breast cancer treatment that had been largely abandoned by oral pathologists despite strong clinical evidence that showed fenretinide can induce cell death, encourage the body's natural cellular defense system and strangle blood supply to tumors.
"The discrepancy between the established efficacy of fenretinide in other cancer types and in oral cancer was puzzling. Then it occurred to me that maybe the structure of the oral mucosa wasn't allowing a therapeutic amount to reach the lesions, even at high doses," says Mallery. "We knew we needed to come up with a way to deliver the therapy directly to the lesion"
In 2009, The Ohio State University College of Dentistry, in collaboration with the Center for Clinical and Translational Science (CCTS) awarded Mallery and her team funding for a project aimed at developing a way to treat precancerous lesions directly in the mouth and preventing recurring lesions.
Mallery partnered with two pharmaceutical chemists from the University of Michigan (Drs. Stephen Schwendeman and Kashappa Goud Desai) along with two Ohio State investigators Drs. Gary Stoner and Peter Larsen to develop a first of its kind patch that could stick to the inside of the mouth, and deliver a continuous therapeutic dose of fenretinide directly on the lesion.
The research team plans to move the patch into pre-clinical and clinical trials, and is already looking at a combination of fenretinide and anthocyanins, as well as testing a combination therapy using the patch and black raspberry-based gel mouthwash to prevent recurrence of lesions.
"If we can effectively treat the lesions with the patch, and then prevent more from coming back, we will completely change - and improve upon - the way oral cancer is currently treated," said Mallery.
Mallery says the best course of action is to prevent oral cancer in the first place, and provides the following tips:
•Use of tobacco products - particularly burned tobacco - is the greatest risk factor for development of oral cancer.
•Watch what you drink and eat. Alcohol consumption - in excess and especially during smoking - can have an additive effect and increase your chances to develop oral cancer. Conversely, a diet high in fruits and vegetables can lower your risk.
•Infection with human papilloma viruses (HPV) causes a subset of oral cancers. Inoculation of both young women and men with the HPV vaccine would markedly decrease HPV-associated oral cancers.
•Remember the mouth heals quickly. If you have a sore in your mouth that doesn't heal in 14 days, seek prompt treatment from your dentist.
•See your dentist at least once a year (better if twice a year) for a complete oral health screening. This is extremely important as oral cancer initially develops a precancerous oral lesions (patient treatment and survival is much better at this stage).
The Ohio State University Center for Clinical and Translational Science