The Ohio State Dental Journal Winter 2021

FAMILY TRAGEDY DRIVES SUSAN R. MALLERY, ’81 DDS, ’90 PHD, TO RESEARCH BREAKTHROUGHS While Dr. Susan R. Mallery was a dental student at Ohio State, she lost her father to small cell carcinoma of the lung, her sister to Hodgkin lymphoma and another sister to an aggressive form of lupus. “I was horribly depressed,” she recalls. “My little nephews had lost their mothers, and I remember thinking, ‘My sisters were doing really wonderful things. This is so unfair.”

Driven forward by the losses in her family and her “hatred of cancer,” Dr. Mallery — now chair of the Division of Oral and Maxillofacial Pathology at the College of Dentistry — has built a prolific research career on the prevention and treatment of oral cancer. After completing her DDS at Ohio State, she practiced dentistry for over a year before her longtime calling toward pathology led her to complete a National Institutes of Health (NIH) research fellowship at Georgetown University. She returned to Ohio State for specialty training in oral pathology, bolstered by a five-year NIH Dental Scientist Award that enabled her to complete her clinical training, earn a PhD in Medical Biochemistry, defend her dissertation concurrently and earn Diplomate status in her specialty.

The focus of her dissertation — biochemical modulators of cell cycle progression to the DNA synthesis “commitment” phase — became the roadmap for her research trajectory that continues to bear fruit today. As a College of Dentistry faculty member since 1990 and a member of the Molecular Carcinogenesis and Chemoprevention Program at Ohio State’s Comprehensive Cancer Center, Dr. Mallery is in the midst of two multimillion R01 awards from NCI/NIH, one of which is a human clinical trial for patients with precancerous oral lesions.

Along with a University of Michigan pharmaceutical chemist colleague, Steve Schwendeman, PhD, Dr. Mallery developed a chemopreventive patch to provide local delivery of fenretinide, a synthetic retinoid derived from vitamin A. Developed by Johnson & Johnson in 1978, fenretinide was designed to re-direct precancerous cells toward regulated, normal growth. “This particular drug was a bench-top chemopreventive rock star,” says Dr. Mallery. “The chemists who designed it knew what they were doing. People thought it was going to be the answer to curing cancer.”

Similar to many chemopreventives, fenretinide’s major challenge is its bioavailability. In pill form, the majority of fenretinide is inactivated during passage through the liver. And in large doses, it causes side effects like impaired night vision, dry skin and mouth, and hyperlipidemia. Fenretinide is also hydrophobic and insoluble in water — presenting unique challenges when delivered in the mouth.

Dr. Mallery worked with Dr. Schwendeman to “take this extremely water-insoluble drug and develop a way to keep it active in a saliva-rich environment, penetrate the surface keratin gain access to the target basal layer cells.” She identified a clinical trial collaborator, ARx Pharma, to develop the final clinical formulation to be used in clinical trials.

ARx’s technical and scientific expertise have resulted in marked patch improvements including enhanced patient comfort and ability for large scale patch production. The team is finishing preclinical animal studies and acquiring the data necessary for submission of an Investigational New Drug (IND) application to the Food and Drug Administration (FDA). Once the IND is in hand, the project will submit an application to the Institutional Review Board (IRB), the final 17