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    Home > Biochemistry News > Biotechnology News > Blocking or deleting a protein could help prevent common oral cancer

    Blocking or deleting a protein could help prevent common oral cancer

    • Last Update: 2022-05-13
    • Source: Internet
    • Author: User
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    Manish V.
    Bais, assistant professor of translational dentistry at Boston University's Goldman School of Dentistry, has identified the lysine-specific demethylase 1 protein as a potential "drugable target" for oral cancer, a finding that may have implications for A day will help doctors remove the tumor
    .

    The most common type of head and neck cancer -- oral squamous cell carcinoma -- like many other cancers, usually starts in harmless situations
    .
    Maybe it's a small white lump in your mouth, or a small red bump on your gums
    .
    Easily overlooked and downplayed
    .
    But then things changed, and the little spot became more ominous and began to grow, invading connective tissue
    .

    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
    .
    But for those less fortunate, the outlook may be bleak: The five-year survival rate for oral squamous cell carcinoma (OSCC) is about 66 percent
    .
    More than 10,000 Americans die each year from oral cancer; smokers and drinkers are hardest hit
    .

    Now, researchers at Boston University's Henry M.
    Goldman School of Dental Medicine have discovered that dialing back -- or even genetically deleting -- a protein that appears to stimulate cancer growth may help limit tumor growth and spread
    .
    Their findings, they say, make the protein, an enzyme called lysine-specific demethylase 1, a potential "drug target" that doctors could target with chemotherapy and immuno-oncology treatment to remove the tumor
    .
    The study was published in the February issue of Molecular Cancer Research
    .

    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.
    Bais, assistant professor of translational dentistry at SDM
    .
    "This research is an important step in the development of new breakthrough oral cancer treatments
    .
    "

    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
    .
    But that's changing.
    "Dental schools have an advantage over traditional cancer centers when it comes to studying the science behind OSCC development," she said, "because we can get precancerous lesions, and cancer centers are basically only seeing complete patients with developing disease
    .

    Helping the Body Fight Back: Anti-Tumor Immunity

    Once the OSCC is established, there is little chance of it being completely eliminated, Bais said
    .
    Clinicians can try chemotherapy and radiation, or even remove the tumor
    .
    "But there's no cure -- you can shrink the tumor, but you can't get rid of it," 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
    .
    "The more severe the tumor, the higher the expression of this protein
    .
    "

    In his lab, Bais set out to test what would happen to tumors on the tongue if LSD1 was blocked
    .
    To limit the enzyme, the researchers either knocked out LSD1 by manipulating the gene to effectively turn it off, or using drugs called small-molecule inhibitors, which enter cells and hinder its normal function
    .
    Small molecule inhibitors have not been used to treat oral cancer in clinical trials for other cancers
    .
    Bais found that disrupting LSD1 suppressed tumor growth
    .

    "The aggressiveness or bad behavior of the tumors went down," he said
    .
    "We found that when we inhibit this protein, it promotes anti-tumor immunity -- our body trying to fight on its own
    .
    "

    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
    .
    Bais says YAP, LSD1 and a few other proteins get caught in a vicious circle, each pushing the other to become more and more aggressive and harmful
    .
    "We need to break the cycle," Bais said
    .

    To find a new way to do this, the researchers combined efforts to inhibit LSD1 with a different inhibitor, a drug called vertiporfin
    .
    Originally developed to help treat serious eye conditions such as macular degeneration, verteporfin is being used by other researchers as a potential cancer treatment, including ovarian cancer
    .
    The combination proved to be effective, Bais said
    .
    He also added a third drug to the mix
    .
    Combining an LSD1 inhibitor with an immune checkpoint inhibitor called an antibody to a 'programmed death 1' ligand, a common immunotherapy drug that helps white blood cells in the immune system kill cancer cells, says Bais, " Showed a good response
    .
    "

    "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
    ," he said.
    Most recently, the National Institute of Dental and Craniofacial Research (NID) and Craniofacial Research) with a $2.
    6 million grant to advance this work
    .
    "While our study is still in the preclinical stage and limited to mice and some human tissues, we hope to expand to human clinical trial samples
    .
    "

    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
    .
    "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
    .
    "

    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
    .
    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
    .

    "So, we can think about disease interception," Kukuruzinska said
    .
    "Maybe also consider how to prevent the occurrence of tumors
    .
    "

    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
    .

    "It's a holy grail," Kukurusinska said of the human samples
    .
    "We can see how they respond to small-molecule inhibitors by taking slices of tumors and trying to treat them with different inhibitors
    .
    "

    Ultimately, it could also open the door to personalized, precision medicine as researchers experiment with different therapies on individual patient tissues
    .
    "It then predicts whether or not the person can be treated with this study," Kukurusinska said
    .
    "That's something we really want to develop
    .
    "

    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
    .
    "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
    .
    In the long run, it can improve the quality of diagnosis and treatment
    .
    "

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