TCD team develop potential new cancer treatment


November 21, 2018

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  • Scientists in Trinity College Dublin (TCD) have developed a potential new treatment for a type of cancer that usually occurs in teenagers and young adults.

    Synovial sarcoma is one of the most common soft tissue cancers found in young people. It usually begins in the arms or legs, although it can affect any part of the body.

    People affected by this type of cancer do not respond well to conventional treatments approaches. Currently, long-term survival rates are well below 50%, so new treatments are urgently needed.

    Using state-of-the-art CRISPR genome screening technology, the TCD scientists first identified that a protein, BRD9, was essential for the survival of synovial sarcoma tumours.

    They then set about designing new drugs to target this protein. Pre-clinical trials in mice showed that a newly developed drug blocks tumour progression, and the next step will be to test this new drug in clinical trials in patients.

    The scientists are hoping these trials will take place soon.

    They pointed out that for years, it has been known that synovial sarcoma is caused by a singular genetic mutation that occurs in 100% of patients. This mutation creates a harmful protein, SS18-SSX, that is responsible for the cancer's development.

    Therefore while scientists reasoned that somehow impeding SS18-SSX would provide an ideal therapy, until now, no such approaches had been developed.

    The TCD team found that BRD9 is essential for the survival of these particular cancer cells. It partners with SS18-SSX to drive the cancer's development. Using this knowledge, the scientists created a new BRD9 ‘degrader' drug, which proved successful in pre-clinical trials in mice.

    "As the term degrader suggests, the drug we created ‘degrades' the BRD9 protein, removing it from cancer cells. It essentially ‘tricks' the cells into eliminating this protein on which they rely, which in turn leads to their death,"

    "Excitingly, our work demonstrates that degrading BRD9 impedes the SS18-SSX protein, which is the underlying cause of synovial sarcoma. We also found that our new drug primarily impacts cellular processes important in synovial sarcoma, but not normal cells. This is very important, because it should result in less unwanted side-effects in patients," explained Dr Gerard Brien of TCD, who is lead author of the research.

    He added that the team hopes that these promising findings ‘will lead to clinical trials of this new drug in patients in the near future'.

    Details of these findings are published in the journal, eLIFE.


    © Medmedia Publications/ 2018