Researchers at New York University College of Dentistry’s (NYU Dentistry) Bluestone Center for Clinical Research have been awarded a two-year National Institutes of Health (NIH) grant to develop biomarkers for tongue cancer, a subset of oral cancers that often are deadly.
“We are investigating the tongue microbiome, which is the bacterial community on the tongue, said Donna Albertson, PhD, grant co-principal investigator, a professor in the Department of Oral and Maxillofacial Surgery at NYU Dentistry, and an investigator at the Bluestone Center for Clinical Research. “We hope to learn how to diagnose aggressive cancers earlier, modulate the microbiome, and prevent or slow the oral cancer progression. Going forward, this research could lead to the development of new, targeted therapies for these cancers.”
The research focus on the oral microbiome is key because the mouth has a lot of diverse bacteria, and disruptions in its normal balance, called “dysbiosis” are considered pivotal in developing diseases of the mouth. New molecular technologies now permit far more comprehensive analyses of the bacterial community in the mouth.
“The majority of oral cavity cancers occur on the tongue,” said co-principal investigator Brian L. Schmidt, DDS, MD, PhD, a professor in the Department of Oral and Maxillofacial Surgery and the director of the Bluestone Center for Clinical Research. “We believe that the cancers develop through a multistep process involving progression through precancerous lesions, with increasing numbers of alterations in the genome.”
The NIH grant, of nearly $450,000, launched on July 1, 2017, and it is funded through June 30, 2019.
Drs. Albertson and Schmidt have already done critically important work in this field. Previously, they discovered a marked increase in Fusobacterium in the mucosal bacteria communities in the oral squamous cell cancer tissue of 13 patients. This increase was not seen on the opposite, unaffected side of the tongue [which served as controls in the patients with oral cancer], nor was it seen in people who do not have oral cancer.
The team then went on to profile changes in the microbiome associated with more than 50 oral cancers. They also studied the genomes of the cancers and were particularly interested in cancers that had acquired extra copies of a small region of the genome, a process called “genome amplification.” Acquisition of extra copies of the genome results in increased expression of genes in the amplified regions to the benefit of the cancer. By profiling the cancer associated bacterial communities and the cancer genomes, they were able to identify a subset of node positive oral tongue cancers with amplification on chromosome 11 and high abundance of Fusobacterium.
“Since we see this amplification of chromosome 11 in some precancers, it may be that these precancer cells interact with Fusobacterium to promote progression to cancer,” explained Dr. Albertson.
The grant combines preclinical and clinical research. Investigators hope that they will be able to translate findings into the clinic rapidly. The team uses next-generation sequencing (a comprehensive set of modern high throughput sequencing technologies) to profile the bacterial community and bioinformatics (computational techniques that permit analysis of complex biological data such as DNA sequences).
Dr. Albertson underscores the significance of using these innovative techniques.
“We now have tools that allow us not only to describe the bacterial and host (cancer) genomes as we have done here, but also to probe further to describe the bacterial phenotype and functional relationships, she said. ”Improvements in these technologies are also yielding results more rapidly and making this research more cost effective,” she said.
The importance of this research is considerable.
In the United States each year, approximately 22,000 Americans are diagnosed with oral cavity cancers, with squamous cell cancers accounting for approximately 90%. Little is known about the natural history of oral squamous cell cancers, making a search for biomarkers and targets a high priority. Surgery is currently the mainstay of treatment, but it often leaves patients with disfigurement, difficulty eating and drinking, and a poor quality of life. Local recurrence, spread, and death occur frequently because the majority of patients are diagnosed with tongue cancer after the cancer has spread to the lymph nodes.
The National Institute of Dental and Craniofacial Research grant award, part of the National Institutes of Health, Grant 1R21DE026964-01A1, is titled “Genome Amplification and Dysbiosis in Cancer.”