The first comprehensive studies of genetic variation in head and neck squamous cell cancers have uncovered mutations that may help refine treatment for patients with the disease, according to researchers at The University of Texas MD Anderson Cancer Center.
The two multi-institutional studies, both published online on the Science Express feature of the journal Science, found:
• Mutations that affect an unexpected tumor-suppressing role of the NOTCH1 gene;
• Infrequent but significant mutations in four suspected cancer-causing genes; and
• Frequent mutation of the tumor-suppressing gene p53, which previously was known to be damaged or impaired in head and neck cancer.
"These findings should help us better treat patients by allowing us to take a more personalized approach than is currently possible with this cancer," said Jeffrey Myers, M.D., Ph.D., professor in MD Anderson's Department of Head and Neck Surgery and co-senior author of one of the papers.
"Long term, we'll see how patients with these genetic mutations do with our conventional treatments of surgery, radiation, chemotherapy or chemoradiation," Myers said. "This will help us identify groups of patients who need additional or different treatments. Also, some of the newly identified mutations might prove to be potential targets for treatment.
"In the near term, we found mutations that increased the activity of PI3K, which is known to be an oncogene in other cancers. There are drugs being studied that target the PI3K pathway, so we might be able to select patients who could benefit from clinical trials of these promising agents," Myers said.
MD Anderson scientists teamed with others from Baylor College of Medicine (BCM) and the Johns Hopkins Kimmel Cancer Center to analyze 32 head and neck tumors. They then validated their findings in another 88 tumor samples. A separate team of researchers from the Broad Institute, Dana-Farber Cancer Institute and the University of Pittsburgh School of Medicine reached the same conclusions based on the analysis of 74 tumors.
About half of head and neck squamous cell cancer patients survive for five years after diagnosis. Disease treatment can disfigure and/or impair breathing, swallowing, speech, taste, hearing or smell. Each year about 50,000 new cases are diagnosed in the United States compared to about 500,000 worldwide.
Prime risk factors for the disease are tobacco and alcohol use, and infection with high-risk subtypes of the human papillomavirus, Myers said. In India, Taiwan and other Asian nations chewing betel or areca nuts also raises the risk of developing oral cancers.