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Scientists have developed a new potential therapeutic approach for synovial sarcoma, one of the most common soft tissue cancers in adolescents and young adults. Currently, the long-term survival rate of patients with synovial sarcoma is well below 50%; a fact that underscores how important new discoveries are to improving the perspectives of patients and their families.
Using state-of-the-art genomic screening CRISPR technology, scientists first identified the protein (BRD9) as essential for the survival of synovial sarcoma tumors. They then designed new drugs to target this protein. Preclinical trials in mice have shown that a newly developed drug blocks tumor progression. The next step will be to test the new drug during clinical trials on patients, which scientists hope to take place in the near future.
Dr. Gerard Brien, genetic researcher at Trinity College Dublin and lead author of the research published in an international journal eLife, aims to identify the "molecular vulnerabilities" of synovial sarcoma tumors. Patients with synovial sarcoma do not respond well to conventional treatment approaches and therefore, like many other difficult-to-treat cancers, have a low survival rate.
Our knowledge of the genetic abnormality at the origin of the disease contradicts our inability to cure synovial sarcoma – it has been known to scientists for years that it is caused by a singular genetic mutation that occurred in 100 years. % patients. This mutation creates a harmful protein (SS18-SSX) responsible for the development of cancer. As a result, scientists felt that an impediment to SS18-SSX would be an ideal treatment. Until now, however, no such approach has been developed.
In this study, Dr. Brien and colleagues used CRISPR-based genomic screening technologies – to perform "genetic screens" – to identify potential therapeutic vulnerabilities of synovial sarcoma tumors. In particular, they discovered a protein (BRD9) essential for synovial sarcoma survival. They confirmed by biochemical studies on synovial sarcoma cells that BRD9 was a partner of the protein causing SS18-SSX disease, and thus supported it in the development of cancer. They then created a new BRD9 "degrade", and in preclinical trials in mice, they discovered that BRD9 degradation blocked the progression of synovial sarcoma tumors.
Dr. Gerard Brien, commenting on this breakthrough, said: "As the term degrader suggests, the drug we created" degrades "the BRD9 protein, eliminating it from cancer cells. 39, eliminate that protein on which they rely., Which leads to their death. "
"Our work demonstrates with enthusiasm that the degradation of BRD9 inhibits the SS18-SSX protein, which is the underlying cause of synovial sarcoma, and that our new drug has an impact on important cellular processes in sarcoma. synovial, but not on normal cells.This is very important because it should result in fewer adverse side effects in patients.We now hope that these promising results will soon lead to clinical trials of this new drug at home. the patients. "
Explore further:
Scientists discover new drug targets in aggressive cancers
More information:
Gerard L Brien et al, Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma, eLife (2018). DOI: 10.7554 / eLife.41305
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