Recent awards from the National Institutes of Health will be used to help researchers at New York University and the University of Pittsburgh investigate some of the cancers that dentists are called upon to treat in their routine practice.
Pain Treatments
The National Institute of Dental and Craniofacial Research at the NIH awarded researchers at New York University a one-year, $369,250 high-priority, short term project award to test whether non-viral gene delivery into oral cancer could be used to treat pain effectively and safely.
“Oral cancer pain is more severe, and the opioid requirement is higher, than pain from any other cancer,” said Dr. Brian L. Schmidt, DDS, MD, PhD, director of the Bluestone Center for Clinical Research and Oral Cancer Center at NYU. “And in the end, pharmacological agents used to treat cancer pain often lack anatomical specificity and produce off-target effects that create additional suffering.”
“We seek to eliminate oral cancer pain by reversing epigenetic changes using gene therapy and set the stage for a new class of medicines that selectively disrupt nociceptive signaling with limited off-target effects,” said Dr. Seiichi Yamano, DDS, PhD, DMD, assistant professor of prosthodontics at the NYU College of Dentistry.
The researchers hypothesize that re-expression of the OPRM1 gene—the gene for the µ -opioid receptor—within oral cancer using non-viral vectors will attenuate cancer pain and restore orofacial function without excessive toxicity. According to Dr. Schmidt, OPRM1 re-expression with viral transduction significantly reduces cancer pain in a mouse model.
“The proposed research is significant because we will use a local delivery technique directly into the cancer to reduce the potential side effects of systemic drugs,” said Dr. Yamano. “Ultimately, these studies might facilitate the development of an effective therapy to treat cancer pain.”
Bone Destruction
The NIH National Cancer Institute (NCI) has awarded the University of Pittsburgh School of Dental Medicine a $2 million, 5-year grant to examine the molecular mechanisms that let multiple myeloma and other cancers destroy bone. Researchers say the project could yield new interventions to prevent bone destruction and slow down primary tumor growth.
Multiple myeloma, which has 100% bone metastasis, tends to prefer craniofacial bones. As a result, nearly 30% of patients are identified through routine dental exams. When a patient’s pain is not relieved through dental treatments for the teeth, for instance, underlying bone destruction may be the cause.
“It is imperative that the young, next generation of dentists understand that dental medicine means treating more than just teeth and extends to the whole head and neck region and even diseases resulting from and affecting other systems,” said Dr. Hongjiao Ouyang, DMD, PhD, associate professor of the departments of Restorative Dentistry/Comprehensive Care and Oral Biology and a member of the Center for Craniofacial Regeneration at the Pitt School of Dental Medicine.
“This bone destruction is a significant cause of pain and mortality in this disease,” said Ouyang. “A better understanding of the molecular pathways that underlie this process could lead us to novel targets for treatment. This could be helpful not only in treatment of multiple myeloma, but also in other cancers that spread to bone, such as breast, prostate, and lung cancer, since various cancers induce similar inflammatory responses in bone.”
The study aims to identify the endoplasmic reticulum stress signaling, a cellular adaptive response to cope with misfolded and unfolded proteins, in bone marrow stromal cells as the pathological mediator that assists cancer in destroying bone. Research will test this pathway using various genetic and pharmacological modalities.
