Blocking or deleting a protein could help prevent common oral cancer

The most common type of head and neck cancer -- oral squamous cell carcinoma -- like many other cancers, usually starts in harmless situations

Those who are fortunate enough to see a dentist before their condition worsens have a chance to stop the lesion from turning into cancer, or at least be sure to start treatment when it is most effective

Now, researchers at Boston University's Henry M.

Considering that at least one-third of Americans don't see their dentist regularly, the finding could be a future savior for those who miss out on preventive care, according to the Centers for Disease Control and Prevention

"These findings have important implications for new and potentially more effective treatments for patients with oral cancer," said study lead author Manish V.

The science behind head and neck cancers has rarely been studied in depth in dental schools in the past, and most research has been done in cancer conducted by the center

Helping the Body Fight Back: Anti-Tumor Immunity

Once the OSCC is established, there is little chance of it being completely eliminated, Bais said

In previous research, I found that lysine-specific demethylase 1 (LSD1) -- an enzyme that normally plays a key role in normal cell and embryonic development is out of control, or "misregulated," in various cancers, including in the head and neck, as well as those in the brain, esophagus, liver and lungs

"The expression of this enzyme goes up with each stage of the tumor," said Bais, who is also a member of Boston University's Center for Multiscale and Translational Mechanobiology

In his lab, Bais set out to test what would happen to tumors on the tongue if LSD1 was blocked

"The aggressiveness or bad behavior of the tumors went down," he said

But LSD1 isn't the only troublemaker in tumors: When it's upregulated, it disrupts a cellular communication process -- the Hippo signaling pathway -- yap -- which normally helps control organ growth and tissue regeneration

To find a new way to do this, the researchers combined efforts to inhibit LSD1 with a different inhibitor, a drug called vertiporfin

"Our findings provide the basis for future clinical studies based on LSD1 inhibition, either as monotherapy or in combination with other drugs in human oral cancer

Predicting Human Success

Byes' focus on oral cancer biology may also help develop other future treatments that are more effective, according to Kukuruzinska
.

"People get really excited when you have a drug that might show some positive initial results, but those studies usually turn to humans, cost billions of dollars, and then end up failing," said Kukuruzinska, who is also an SDM Director of the Predoctoral Research Program and Professor of Translational Dental Medicine
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"If you really understand which pathways, which cellular processes are affected by these inhibitors, then it can allow you to predict in advance whether you will be successful in human patients
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At Boston University, the School of Dentistry has a teaching clinic and shares a campus with Boston University School of Medicine and its main teaching hospital, Boston Medical Center
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It is also home to the Bururi University Head and Neck Cancer Program, which pairs basic science researchers with clinicians to study the underlying mechanisms of oral cancer, and the Centre for Oral Diseases, a multidisciplinary clinical research collaboration
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"So, we can think about disease interception," Kukuruzinska said
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"Maybe also consider how to prevent the occurrence of tumors
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With head and neck surgeons in the clinic and nearby hospitals, researchers like Bais can test any new treatments and methods on human tissue samples
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"It's a holy grail," Kukurusinska said of the human samples
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"We can see how they respond to small-molecule inhibitors by taking slices of tumors and trying to treat them with different inhibitors
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Ultimately, it could also open the door to personalized, precision medicine as researchers experiment with different therapies on individual patient tissues
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"It then predicts whether or not the person can be treated with this study," Kukurusinska said
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"That's something we really want to develop
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Having students involved in a number of research projects — three of which are co-authors on Bais' papers and another with Thabet Alhousami (SDM'22) as lead author — means that future dentists at Boston University will enter the clinic with a sharper eye , look for potentially malicious bumps and smudges
.

"They will be able to say, 'This is a precancer or cancer,' and that will affect their diagnosis," Bais said
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"Then, in terms of treatment, because they now know what works and what immunotherapy works, they can refer specifically to where the patient should go next
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In the long run, it can improve the quality of diagnosis and treatment
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"