• Biological pathways found that drive gen

    From ScienceDaily@1:317/3 to All on Thu Apr 28 22:30:46 2022
    Biological pathways found that drive genomic changes and bone metastasis
    in ewing sarcoma, a rare childhood cancer

    Date:
    April 28, 2022
    Source:
    Georgetown University Medical Center
    Summary:
    In studies using mice grafted with human Ewing sarcoma tissue,
    researchers have identified a biological pathway that is activated
    when tissue is starved of oxygen due to rapid growth of a tumor,
    thereby allowing cancer cells to make genetic changes so they
    can metastasize to the bone and thrive even when exposed to
    chemotherapy.



    FULL STORY ==========================================================================
    In studies using mice grafted with human Ewing sarcoma tissue, researchers
    from Georgetown University Medical Center and colleagues have identified
    a biological pathway that is activated when tissue is starved of oxygen
    due to rapid growth of a tumor, thereby allowing cancer cells to make
    genetic changes so they can metastasize to the bone and thrive even when exposed to chemotherapy.


    ==========================================================================
    The pathway the scientists identified involves a receptor on the
    surface of a cancer cell, called Y5R, which plays a role in mediating oxygen-deprivation effects -- if it was blocked or turned off, genetic
    changes would be limited, thereby inhibiting metastasis of a tumor.

    The finding appeared April 28, 2022, in Nature Communications.

    Each year, about 200 children and young adults in the United States are diagnosed with a Ewing tumor. About half of all Ewing sarcoma diagnoses
    are in people between the ages of 10 and 20; almost all cases of Ewing
    sarcoma occur in white and Hispanic people. If the tumor has spread to
    distant areas at the time of diagnosis, the 5-year survival rate is 38
    percent but if it spreads to the bone, survival drops to between 8 to
    14 percent.

    "While the role of rapid genetic changes in spurring the growth of
    cancer is well known, the mechanisms initiating these changes are not
    well understood and strategies to prevent them are lacking," says
    Joanna Kitlinska, PhD, an associate professor in the Department of
    Biochemistry and Molecular & Cellular Biology at Georgetown University
    and corresponding author of the study. "That's why our identification of
    Y5R's involvement in initiating such genetic alterations is important
    as it gives us a target to aim at or block that could avert cancer
    genome evolution and resulting progression to metastatic tumors that
    are resistant to chemotherapy." The current standard-of-care for Ewing
    sarcoma involves systemic cell-killing chemotherapy which can affect
    all cells in the body leading to side effects.

    There are no treatments targeted at genetic alterations that are used
    in routine treatment of Ewing sarcoma, which might make treatments less
    toxic. In particular, adequate treatments for patients with metastatic
    disease are lacking.

    There are currently a number of drugs available that target Y5R
    because it's also implicated in regulating food intake and psychiatric disorders. Several Y5R-targeted drugs have been successfully used in
    animal studies; one of them was used in human clinical trials for
    obesity. However, most of them are designed to block functions in
    the brain that inhibit food intake. According to Kitlinska, the main
    challenge will be to design Y5R-targeted drugs that do not cross the blood-brain barrier as these effects are undesirable in cancer patients.

    "We will keep performing experiments in mice in order to try to
    identify the mechanisms triggering spread of Ewing to the bone," says Kitlinska. "Findings in Ewing sarcoma may also be relevant to other
    cancer types known to have high expression levels of Y5R, including
    another pediatric cancer, neuroblastoma, as well as common adulthood malignancies, such as breast, prostate and liver cancers."

    ========================================================================== Story Source: Materials provided by
    Georgetown_University_Medical_Center. Note: Content may be edited for
    style and length.


    ========================================================================== Journal Reference:
    1. Congyi Lu, Akanksha Mahajan, Sung-Hyeok Hong, Susana Galli,
    Shiya Zhu,
    Jason U. Tilan, Nouran Abualsaud, Mina Adnani, Stacey Chung, Nada
    Elmansy, Jasmine Rodgers, Olga Rodriguez, Christopher Albanese,
    Hongkun Wang, Maureen Regan, Valerie Zgonc, Jan Blancato, Ewa
    Krawczyk, G. Ian Gallicano, Michael Girgis, Amrita Cheema, Ewa
    Iżycka- Świeszewska, Luciane R. Cavalli, Svetlana D. Pack,
    Joanna Kitlinska.

    Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers
    chromosomal instability and bone metastasis in Ewing sarcoma. Nature
    Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29898-x ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220428085649.htm

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