Researchers at New York University (NYU) Oral Cancer Center were awarded a $2.5 million grant (R01CA228525) from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), to study the role of artemin in oral cancer pain and growth. The principal investigators, Donna Albertson, PhD, and Brian Schmidt, DDS, MD, PhD, seek to improve oral cancer treatment and alleviate pain by targeting overexpressed cancer mediators.
Albertson and Schmidt initiated their investigation of artemin-;a protein encoded by a gene of the same name- when a molecular analysis of oral cancers from patients seen at the NYU Oral Cancer Center revealed elevated concentrations of artemin in tumors of the patients with pain. Since Schmidt founded the NYU Oral Cancer Center in 2013, scores of oral cancer patients have volunteered to participate in an ongoing investigation of why cancers hurt. Prior to surgery, Schmidt measures pain with a written patient questionnaire. A sample of the patient's cancer is collected during surgery and molecularly compared with normal oral tissue. After analyzing the questionnaire and molecular data, Albertson and Schmidt discovered a strong correlation between artemin levels and pain. Since artemin is overexpressed in oral cancers, it is likely that artemin also promotes cancer growth.
Out of tens of thousands of genes, the gene that codes for artemin is one that is highly expressed in oral cancer compared with normal tissue. Artemin became the obvious target to simultaneously address cancer growth and pain."
Donna Albertson, professor of oral and maxillofacial surgery at NYU College of Dentistry
Following their discovery in the tissues of oral cancer patients, Albertson and Schmidt undertook experiments in the laboratory to confirm the role of artemin in both cancer pain and cancer growth.
Artemin is one of four members of the glial cell line-derived-neurotrophic factor (GDNF) family of proteins. Neurotrophins are secreted molecules that promote growth, differentiation, and survival of neurons. Artemin contributes to pain by inducing expression of receptors on sensory neurons.
Oral cancer patients endure severe chronic pain during everyday functions such as chewing and speaking. Albertson and Schmidt have investigated oral cancer pain at the molecular level over the last 13 years to alleviate pain in these patients through improved pharmacologic therapy.
"I am unable to adequately manage oral cancer pain with the therapies that are currently available," said Schmidt, professor of oral and maxillofacial surgery at NYU College of Dentistry and director of the NYU Oral Cancer Center. "Ever greater opioid doses are required as drug tolerance develops. Debilitating side effects degrade quality of life in a population of patients who also face an ominous five-year survival rate."
Cancer pain is attributed to secretion of mediators into the cancer environment. Cancer-derived mediators sensitize pain signaling neurons. Cancers also induce growth of neurons in the tumor. Subsequently there is greater interaction between these mediators and neurons. Overexpressed artemin may also act as an oncogene to promote cancer growth. In their newly funded research, Albertson and Schmidt will evaluate how overexpression of artemin contributes to tumor growth as well as pain secondary to changes in neuronal function.