Trinity researchers have developed a new therapeutic approach to treating a common form of soft-tissue cancer, an illness that affects teenagers and young adults.
Synovial sarcoma, which typically occurs in the arms and legs, forms in cartilage, fat, muscle, blood vessels and in the supportive tissues of the body. Synovial sarcoma has a long-term survival rate of below 50 per cent.
Dr Gerard Brien, a research fellow in genetics in Trinity and the lead author of the research, set out to identify “molecular vulnerabilities” in these tumours. Finding these vulnerabilities could provide possible targets for cancer treatment.
Brien’s team used a highly advanced DNA-editing tool, called CRISPR, which is used to change how our genes work. This technology allowed the researchers to identify a protein, called BRD9, which is essential for the survival of synovial sarcoma tumours. The team then began developing new drugs to target this protein with the aim of inhibiting it, thus killing the tumour.
Pre-clinical trials in mice have shown that the newly developed drug stops the progression of tumours. The drug will now have to be tested in clinical trials in patients to test its effectiveness in humans.
Despite its low survival rates and lack of a cure, synovial sarcoma has been known to be caused by a mutation in a single gene that occurs in all its patients. The mutation produces a harmful protein called SS18-SSX which is responsible for cancer development. This protein has therefore been regarded as a target for cancer therapy, with Brien’s team putting forward the first possible approach.
The team confirmed that the BRD9 protein works in conjunction with the SS18-SSX protein to drive cancer development. Building on this discovery, Brien’s team created a new BRD9 “degrader” drug, which degrades the protein and removes it from cancer cells.
Commenting on the breakthrough, Brien said in a press release: “It essentially ‘tricks’ the cells into eliminating this protein on which they rely, which in turn leads to their death.”
This drug successfully blocked synovial sarcoma tumour progression in mice trials. It also targets processes that are important in the tumour cells but not normal body cells. This is important in terms of targeting the cancerous cells specifically and reducing the risk of side effects.
Brien is the 2018 Irish Cancer Society Biomedical Research Fellow and recently returned to Trinity to establish his own research laboratory.
