“Our study suggests that a gene’s role can depend on the tumor type. In some cases, a gene can act as a growth promoter in cancer, and in other cases, such as head and neck cancer, the same gene behaves as a growth suppressor,” said Kinzler.

Efforts to combat the mutated p53 tumor suppressor gene with targeted drugs, for example, have so far been unsuccessful.

The next step based on these novel head and neck cancer discoveries, the scientists agree, is to tease out how the genes function in normal cells, whether they form the lining of the larynx, pharynx, or another anatomical site affected by head and neck cancer.

“Both of our studies reveal few clues to the significance of NOTCH mutations. Further studies will be necessary to define its role in prognosis, diagnosis, and/or treatment,” said Nishant Agrawal, a head and neck surgical oncologist at Johns Hopkins and a lead author of one of the Science papers. “The idea is to use these genetic alterations to predict a patient’s prognosis and define personalized treatment strategies tailored to their cancer’s genome.”

Both teams confirmed the role of HPV infection in head and neck cancer, particularly oropharyngeal cancer. Thought to be transmitted by oral sex, the infection has become more prominent. The studies reveal that HPV-positive tumors carried fewer mutations than HPV-negative tumors. Patients with HPV-positive head and neck cancers tend to fare better than patients whose cancers are not caused by the virus.

Translating these discoveries into therapies for patients will take more studies and more time, the scientists all said, but the revelations set a course for the future.

Jeffrey N. Myers, professor of head and neck surgery at M. D. Anderson, said both groups’ work highlights the complexity of the disease and its multiple gene abnormalities.

“It has told us new things that will give us both clinical and scientific opportunities to study in the near and long term,” Myers said. “I think that we’re also in a position to design very specific clinical studies to further understand the significance of these mutations, as well as to begin to think about potentially targeting some of the abnormalities.”

Those studies could include looking at patients with different mutations in addition to p53 and the NOTCH family to see how well they fare.

“The race will be on to figure out the function and particularly the therapeutically relevant function of these mutations,” Grandis said.

Agrawal said the collaborative effort is necessary.

“I think it’s great we are advancing head and neck cancer research this way,” he said. “Unfortunately, the cancer has been beating us. Now it’s time for us to take a permanent lead.”

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